Publications

NOTE:

Due to a change in job location by JVF, currently director of the Superior Polytechnical School at University of Vic, this site is currently on hold for the length of such assignment. The site will be kept up to date with respect to academic and research activity, but will not represent the current work by JVF

JVF ResearcherID: C-7127-2009

Journal articles
MSc and PhD thesis
Book chapters
Other

Journal Articles

[2012,article] bibtex

J. Dalton, O. Kalid, M. Schushan, N. Ben-Tal, and J. Villà–Freixa, "New model of CFTR proposes active channel-like conformation," J. Chem. Inf. Model., vol. 52(7), pp. 1842-1853, 2012.

@article{Dalton2012, author = {Dalton, James and Kalid, Ori and Schushan, Maya and Ben-Tal, Nir and Vill\`a--Freixa, Jordi}, title = {{New model of CFTR proposes active channel-like conformation}}, year = {2012}, journal={{J. Chem. Inf. Model.}}, volume = {52(7)}, pages = {1842--1853}, url = {http://www.ncbi.nlm.nih.gov/pubmed/22747419} }
[2012,article] bibtex

P. Margalef, V. Fernández-Majada, A. Villanueva, R. Garcia-Carbonell, M. Iglesias, L. López, M. Martínez-Iniesta, J. Villà-Freixa, M. C. Mulero, M. Andreu, F. Torres, M. W. Mayo, A. Bigas, and L. Espinosa, "A novel truncated form of IKK$\alpha$ is responsible for nuclear IKK activity in colorectal cancer," Cell Rep., vol. 2, pp. 840-854, 2012.

@article{Margalef2012, author = {Pol Margalef and Vanessa Fern\'andez-Majada and Alberto Villanueva and Ricard Garcia-Carbonell and Mar Iglesias and Laura L\'opez and Mar\'ia Mart\'inez-Iniesta and Jordi Vill\`a-Freixa and Mari Carmen Mulero and Montserrat Andreu and Ferran Torres and Marty W. Mayo and Anna Bigas and Llu\'is Espinosa}, title = {{A novel truncated form of IKK$\alpha$ is responsible for nuclear IKK activity in colorectal cancer}}, year = {2012}, journal={{Cell Rep.}}, volume = {2}, pages = {840-854}, doi = {10.1016/j.celrep.2012.08.028}, url = {http://www.cell.com/cell-reports/abstract/S2211-1247(12)00268-9} }
[2011,article] bibtex

D. Maier, W. Kalus, M. Wolff, S. G. Kalko, J. Roca, I. M. Mas, N. Turan, M. Cascante, F. Falciani, M. Hernández, J. Villà-Freixa, and S. Losko, "Knowledge Management for Systems Biology; a general and visually driven framework applied to translational medicine," BMC Syst. Biol., vol. 5, p. 38, 2011.

@ARTICLE{Maier2010, author = {Dieter Maier and Wenzel Kalus and Martin Wolff and Susana G. Kalko and Josep Roca and Igor Mar�n de Mas and Nil Turan and Marta Cascante and Francesco Falciani and Miguel Hern\'andez and Jordi Vill\`a-Freixa and Sascha Losko}, title = {{Knowledge Management for Systems Biology; a general and visually driven framework applied to translational medicine}}, journal = {BMC Syst. Biol.}, volume = {5}, pages = {38}, year = {2011}, url = {http://www.biomedcentral.com/1752-0509/5/38} }
[2011,article] bibtex

P. V. Lawford, A. V. Narracott, K. McCormack, J. Bisbal, C. Martin, B. Bijnens, B. Brook, M. Zachariou, J. Villà–Freixa, P. Kohl, K. Fletcher, and V. Diaz-Zuccarini, "Virtual physiological human: training challenges," Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences, vol. 369, iss. 1935, p. 494, 2011.

@article{Lawford2011, author = {Lawford, Patricia V. and Narracott, Andrew V. and McCormack, Keith and Bisbal, Jesus and Martin, Carlos and Bart Bijnens and Brook, Bindi and Zachariou, Margarita and Jordi Vill\`a--Freixa and Kohl, Peter and Fletcher, Katherine and Diaz-Zuccarini, Vanessa}, title = {{Virtual physiological human: training challenges}}, volume = {369}, number = {1935}, pages = {494}, year = {2011}, doi = {10.1098/rsta.2010.0307}, URL = {http://rsta.royalsocietypublishing.org/content/369/1935/494.long}, journal = {Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences} }
[2011,article] bibtex

C. Ávila, N. Drechsel, R. Alcántara, and J. Villà-Freixa, "Multiscale Simulations of Protein Aggregation," Curr. Prot. Pept. Sci., vol. 12, pp. 221-234, 2011.

@ARTICLE{Avila2011, author = {C\'esar \'Avila and Nils Drechsel and Ra\'ul Alc\'antara and Jordi Vill\`a-Freixa}, title = {{Multiscale Simulations of Protein Aggregation}}, journal = {Curr. Prot. Pept. Sci.}, year = {2011}, volume = {12}, pages = {221--234}, url = {http://www.ncbi.nlm.nih.gov/pubmed/21348836} }
[2011,article] bibtex

G. Jaña, V. Jiménez, J. Villà-Freixa, X. Prat-Resina, E. Delgado, and J. Alderete, "A QM/MM Study of the Last Two Steps of the Catalytic Cycle of Acetohydroxyacid Synthase," Computational and Theoretical Chemistry, vol. 966, pp. 159-166, 2011.

@ARTICLE{Jana2011, author = {Gonzalo Ja\~na and Ver\'onica Jim\'enez and Jordi Vill\`a-Freixa and Xavier Prat-Resina and Eduardo Delgado and Joel Alderete}, title = {{A QM/MM Study of the Last Two Steps of the Catalytic Cycle of Acetohydroxyacid Synthase}}, journal = {Computational and Theoretical Chemistry}, volume = {966}, pages = {159--166}, url = {http://dx.doi.org/10.1016/j.comptc.2011.02.030}, year = {2011} }
[2011,article] bibtex

J. Villà–Freixa, "Simulacions moleculars de la recativitat enzimàtica: dissecant contribucions amb l’ajut d’un ordinador," Omnis Cellula, vol. 26, p. 8, 2011.

@article{VillaFreixa2011, author = {Jordi Vill\`a--Freixa}, title = {{Simulacions moleculars de la recativitat enzim\`atica: dissecant contribucions amb l'ajut d'un ordinador}}, year = {2011}, journal={{Omnis Cellula}}, volume = {26}, pages = {8}, url = {http://publicacions.iec.cat/PopulaFitxa.do?moduleName=revistes_cientifiques&subModuleName=&idColleccio=215} }
[2010,article] bibtex

J. Cooper, F. Cervenansky, G. de Fabritiis, J. Fenner, D. Friboulet, T. Giorgino, S. Manos, Y. Martelli, J. Villà–Freixa, S. Zasada, S. Lloyd, K. McCormack, and P. V. Coveney, "The Virtual Physiological Human Toolkit," Phil. Trans. R. Soc. A, vol. 368, pp. 3925-3936, 2010.

@ARTICLE{Cooper2010, author = {Johnathan Cooper and Frederic Cervenansky and Gianni de Fabritiis and John Fenner and Denis Friboulet and Toni Giorgino and Steven Manos and Yves Martelli and Jordi Vill\`a--Freixa and Stefan Zasada and Sharon Lloyd and Keith McCormack and Peter V. Coveney}, title = {{The Virtual Physiological Human Toolkit}}, journal = {Phil. Trans. R. Soc. A}, year = {2010}, volume = {368}, pages = {3925--3936}, url = {http://www.ncbi.nlm.nih.gov/pubmed/20643685} }
[2010,article] bibtex

P. Rué, J. Villà–Freixa, and K. Burrage, "Simulation Methods with Extended Stability for Stiff Biochemical Kinetics," BMC Syst. Biol., vol. 4, p. 110, 2010.

@ARTICLE{Rue2010, author = {Pau Ru\'e and Jordi Vill\`a--Freixa and Kevin Burrage}, title = {{Simulation Methods with Extended Stability for Stiff Biochemical Kinetics}}, journal = {BMC Syst. Biol.}, year = {2010}, volume = {4}, pages = {110}, doi = {10.1186/1752-0509-4-110}, url = {http://www.biomedcentral.com/1752-0509/4/110} }
[2010,article] bibtex

G. Jaña, V. Jiménez, J. Villà-Freixa, X. Prat-Resina, E. Delgado, and J. Alderete, "Computational study on the carboligation reaction of acetohidroxyacid synthase: new approach on the role of the HEThDP- intermediate.," Proteins, vol. 78, iss. 7, pp. 1774-1788, 2010.

@ARTICLE{Jana2010, author = {Gonzalo Ja\~na and Ver\'onica Jim\'enez and Jordi Vill\`a-Freixa and Xavier Prat-Resina and Eduardo Delgado and Joel Alderete}, title = {Computational study on the carboligation reaction of acetohidroxyacid synthase: new approach on the role of the HEThDP- intermediate.}, journal = {Proteins}, year = {2010}, volume = {78}, pages = {1774--1788}, number = {7}, month = {May}, abstract = {Acetohydroxyacid synthase (AHAS) is a thiamin diphosphate dependent enzyme that catalyses the decarboxylation of pyruvate to yield the hydroxyethyl-thiamin diphosphate (ThDP) anion/enamine intermediate (HEThDP(-)). This intermediate reacts with a second ketoacid to form acetolactate or acetohydroxybutyrate as products. Whereas the mechanism involved in the formation of HEThDP(-) from pyruvate is well understood, the role of the enzyme in controlling the carboligation reaction of HEThDP(-) has not been determined yet. In this work, molecular dynamics (MD) simulations were employed to identify the aminoacids involved in the carboligation stage. These MD studies were carried out over the catalytic subunit of yeast AHAS containing the reaction intermediate (HEThDP(-)) and a second pyruvate molecule. Our results suggest that additional acid-base ionizable groups are not required to promote the catalytic cycle, in contrast with earlier proposals. This finding leads us to postulate that the formation of acetolactate relies on the acid-base properties of the HEThDP(-) intermediate itself. PM3 semiempirical calculations were employed to obtain the energy profile of the proposed mechanism on a reduced model of the active site. These calculations confirm the role of HEThDP(-) intermediate as the ionizable group that promotes the carboligation and product formation steps of the catalytic cycle.}, doi = {10.1002/prot.22693}, institution = {Grupo de Qu�mica Te�rica y Computacional, Facultad de Ciencias Qu�micas, Universidad de Concepci�n, Casilla 160-C, Concepci�n, Chile.}, owner = {jvilla}, pmid = {20225259}, timestamp = {2010.04.22}, url = {http://dx.doi.org/10.1002/prot.22693} }
[2010,article] bibtex

A. L. García–Lomana, Q. Beg, G. de Fabritiis, and J. Villà–Freixa, "Statistical Analysis of Global Connectivity and Activity Distributions in Cellular Networks," J. Comput. Biol., vol. 17(7), pp. 869-878, 2010.

@ARTICLE{Garcia2010, author = {Adri\'an L. Garc\'ia--Lomana and Qasim Beg and Gianni de Fabritiis and Jordi Vill\`a--Freixa}, title = {Statistical Analysis of Global Connectivity and Activity Distributions in Cellular Networks}, journal = {J. Comput. Biol.}, year = {2010}, volume = {17(7)}, pages = {869--878}, abstract = {Various molecular interaction networks have been claimed to follow power-law decay for their global connectivity distribution. It has been proposed that there may be underlying generative models that explain this heavy-tailed behavior by self-reinforcement processes such as classical or hierarchical scale-free network models. Here we analyze a comprehensive data set of protein-protein and transcriptional regulatory interaction networks in yeast, an \textit{E. coli} metabolic network, and gene activity profiles for different metabolic states in both organisms. We show that in all cases the networks have a heavy-tailed distribution, but most of them present significant differences from a power-law model according to a stringent statistical test. Those few data sets that have a statistically significant fit with a power-law model follow other distributions equally well. Thus, while our analysis supports that both global connectivity interaction networks and activity distributions are heavy-tailed, they are not generally described by any specific distribution model, leaving space for further inferences on generative models.}, url = {http://arxiv.org/abs/1004.3138} }
[2009,article] bibtex

J. Scheper, B. Oliva, J. Villà-Freixa, and T. M. Thomson, "Analysis of electrostatic contributions to the selectivity of interactions between RING-finger domains and ubiquitin-conjugating enzymes.," Proteins, vol. 74, iss. 1, pp. 92-103, 2009.

@ARTICLE{Scheper2009, author = {Johanna Scheper and Baldo Oliva and Jordi Vill\`a-Freixa and Timothy M Thomson}, title = {Analysis of electrostatic contributions to the selectivity of interactions between RING-finger domains and ubiquitin-conjugating enzymes.}, journal = {Proteins}, year = {2009}, volume = {74}, pages = {92--103}, number = {1}, month = {Jan}, abstract = {The zinc-coordinated protein motifs known as RING-finger domains, present on a class of ubiquitin ligases (E3's), recruit ubiquitin-conjugating enzymes (E2s), tethering them to substrate proteins for covalent modification with ubiquitin. Each RING-finger domain can recruit different E2s, and these interactions are frequently selective, in that certain RING-finger domains associate preferentially with certain E2s. This selectivity acquires particular biological relevance when the recruited E2s exert specialized functions. We have explored the determinants that specify the presence or absence of experimentally detectable interaction between two RING-finger domains, those on RNF11 and RNF103, and two E2s, UBC13, a specialized E2 that catalyzes ubiquitin chain elongation through Lys63 of ubiquitin, and UbcH7, which mediates polyubiquitylation through Lys48. Through the iterative use of computational predictive tools and experimental validations, we have found that these interactions and their selectivity are partly governed by the combinations of electrostatic interactions linking specific residues of the contact interfaces. Our analysis also predicts that the main determinants of selectivity of these interactions reside on the RING-finger domains, rather than on the E2s. The application of some of these rules of interaction selectivity has permitted us to experimentally manipulate the selectivity of interaction of the RING-finger domain-E2 pairs under study.}, doi = {10.1002/prot.22120}, institution = {Department of Molecular and Cell Biology, Instituto de Biolog�a Molecular de Barcelona, Consejo Superior de Investigaciones Cient�ficas, Barcelona, Spain.}, keywords = {Binding Sites; Carrier Proteins, chemistry/metabolism; Humans; Models, Chemical; Nerve Tissue Proteins, chemistry/metabolism; Point Mutation; Protein Binding; RING Finger Domains; Simulation; Static Electricity; Ubiquitin-Conjugating Enzymes, metabolism; Ubiquitin-Protein Ligases, metabolism}, owner = {jordivilla}, pmid = {18615712}, timestamp = {2010.03.14}, url = {http://dx.doi.org/10.1002/prot.22120} }
[2009,article] bibtex

F. X. Guix, G. Ill-Raga, R. Bravo, T. Nakaya, G. de Fabritiis, M. Coma, G. P. Miscione, J. Villà-Freixa, T. Suzuki, X. Fernandez-Busquets, M. A. Valverde, B. de Strooper, and F. J. Munoz, "Amyloid-dependent triosephosphate isomerase nitrotyrosination induces glycation and tau fibrillation," Brain, vol. 132, iss. 5, pp. 1335-1345, 2009.

@ARTICLE{Guix2009, author = {Guix, Francesc X. and Ill-Raga, Gerard and Bravo, Ramona and Nakaya, Tadashi and de Fabritiis, Gianni and Coma, Mireia and Miscione, Gian Pietro and Vill\`a-Freixa, Jordi and Suzuki, Toshiharu and Fernandez-Busquets, Xavier and Valverde, Miguel A. and de Strooper, Bart and Munoz, Francisco J.}, title = {{Amyloid-dependent triosephosphate isomerase nitrotyrosination induces glycation and tau fibrillation}}, journal = {Brain}, year = {2009}, volume = {132}, pages = {1335-1345}, number = {5}, abstract = {Alzheimer's disease neuropathology is characterized by neuronal death, amyloid {beta}-peptide deposits and neurofibrillary tangles composed of paired helical filaments of tau protein. Although crucial for our understanding of the pathogenesis of Alzheimer's disease, the molecular mechanisms linking amyloid {beta}-peptide and paired helical filaments remain unknown. Here, we show that amyloid {beta}-peptide-induced nitro-oxidative damage promotes the nitrotyrosination of the glycolytic enzyme triosephosphate isomerase in human neuroblastoma cells. Consequently, nitro-triosephosphate isomerase was found to be present in brain slides from double transgenic mice overexpressing human amyloid precursor protein and presenilin 1, and in Alzheimer's disease patients. Higher levels of nitro-triosephosphate isomerase (P < 0.05) were detected, by Western blot, in immunoprecipitates from hippocampus (9 individuals) and frontal cortex (13 individuals) of Alzheimer's disease patients, compared with healthy subjects (4 and 9 individuals, respectively). Triosephosphate isomerase nitrotyrosination decreases the glycolytic flow. Moreover, during its isomerase activity, it triggers the production of the highly neurotoxic methylglyoxal (n = 4; P < 0.05). The bioinformatics simulation of the nitration of tyrosines 164 and 208, close to the catalytic centre, fits with a reduced isomerase activity. Human embryonic kidney (HEK) cells overexpressing double mutant triosephosphate isomerase (Tyr164 and 208 by Phe164 and 208) showed high methylglyoxal production. This finding correlates with the widespread glycation immunostaining in Alzheimer's disease cortex and hippocampus from double transgenic mice overexpressing amyloid precursor protein and presenilin 1. Furthermore, nitro-triosephosphate isomerase formed large {beta}-sheet aggregates in vitro and in vivo, as demonstrated by turbidometric analysis and electron microscopy. Transmission electron microscopy (TEM) and atomic force microscopy studies have demonstrated that nitro-triosephosphate isomerase binds tau monomers and induces tau aggregation to form paired helical filaments, the characteristic intracellular hallmark of Alzheimer's disease brains. Our results link oxidative stress, the main etiopathogenic mechanism in sporadic Alzheimer's disease, via the production of peroxynitrite and nitrotyrosination of triosephosphate isomerase, to amyloid {beta}-peptide-induced toxicity and tau pathology.}, doi = {10.1093/brain/awp023}, eprint = {http://brain.oxfordjournals.org/cgi/reprint/132/5/1335.pdf}, url = {http://brain.oxfordjournals.org/cgi/content/abstract/132/5/1335} }
[2008,article] bibtex

L. G. A. de Lomana, À. Gómez-Garrido, D. Sportouch, and J. Villà-Freixa, "Optimal Experimental Design in the Modelling of Pattern Formation," LNCS, vol. 5101, pp. 610-619, 2008.

@ARTICLE{Lomana2008, author = {A. L\'{o}pez Garc\'{i}a de Lomana and \`{A}. G\'{o}mez-Garrido and D. Sportouch and J. Vill\`{a}-Freixa}, title = {Optimal Experimental Design in the Modelling of Pattern Formation}, journal = {LNCS}, year = {2008}, volume = {5101}, pages = {610-619}, url = {http://www.springerlink.com/content/kk7774170666m254/fulltext.pdf} }
[2008,article] bibtex

D. G. Fabritiis, P. V. Coveney, and J. Villà-Freixa, "Energetics of K+ permeability through Gramicidin A by forward-reverse steered molecular dynamics.," Proteins, vol. 73, iss. 1, pp. 185-194, 2008.

@ARTICLE{Fabritiis2008, author = {G. De Fabritiis and P. V. Coveney and J. Vill\`a-Freixa}, title = {Energetics of K+ permeability through Gramicidin A by forward-reverse steered molecular dynamics.}, journal = {Proteins}, year = {2008}, volume = {73}, pages = {185--194}, number = {1}, month = {Oct}, abstract = {The estimation of ion channel permeability poses a considerable challenge for computer simulations because of the significant free energy barriers involved, but also offers valuable molecular information on the ion permeation process not directly available from experiments. In this article we determine the equilibrium free energy barrier for potassium ion permeability in Gramicidin A in an efficient way by atomistic forward-reverse non-equilibrium steered molecular dynamics simulations, opening the way for its use in more complex biochemical systems. Our results indicate that the tent-shaped energetics of translocation of K+ ions in Gramicidin A is dictated by the different polarization responses to the ion of the external bulk water and the less polar environment of the membrane.}, doi = {10.1002/prot.22036}, institution = {Computational Biochemistry and Biophysics Laboratory (GRIB-IMIM), Universitat Pompeu Fabra, Barcelona Biomedical Research Park, C/Dr Aiguader 88, 08003 Barcelona, Spain. gianni.defabritiis@upf.edu}, keywords = {Computer Simulation; Gramicidin, chemistry/metabolism; Ion Channels, chemistry/metabolism; Ion Transport; Models, Molecular; Permeability; Potassium, chemistry; Thermodynamics}, owner = {jvilla}, pmid = {18412256}, timestamp = {2010.01.03}, url = {http://dx.doi.org/10.1002/prot.22036} }
[2007,article] bibtex

G. de Fabritiis, J. Villà-Freixa, and P. V. Coveney, "Multiscale modelling of permeation through membrane channels using pregenerated molecular dynamics trajectories," Int. J. Mod. Phys. C, vol. 18, pp. 511-518, 2007.

@ARTICLE{Fabritiis2007a, author = {de Fabritiis, G. and Vill\`a-Freixa, J. and Coveney, P. V.}, title = {{Multiscale modelling of permeation through membrane channels using pregenerated molecular dynamics trajectories}}, journal = {Int. J. Mod. Phys. C}, year = {2007}, volume = {18}, pages = {511--518}, url = {http://www.worldscinet.com/ijmpc/18/1804/S0129183107010747.html} }
[2007,article] bibtex

M. A. Johnston and J. Villà-Freixa, "Enabling Data Sharing and Collaboration in Complex Systems Applications," LNBI, vol. 4360, pp. 124-140, 2007.

@ARTICLE{Johnston2007, author = {Johnston, M.A. and Vill\`a-Freixa, J.}, title = {{Enabling Data Sharing and Collaboration in Complex Systems Applications}}, journal = LNBI, year = {2007}, volume = {4360}, pages = {124--140}, timestamp = {2008.12.02}, url = {http://www.springerlink.com/content/9476700461j37732} }
[2006,article] bibtex

J. Bonet, G. Caltabiano, A. K. Khan, M. A. Johnston, C. Corbí, A. Gómez, X. Rovira, J. Teyra, and J. Villà-Freixa, "The role of residue stability in transient protein-protein interactions involved in enzymatic phosphate hydrolysis. A computational study.," Proteins, vol. 63, iss. 1, pp. 65-77, 2006.

@ARTICLE{Bonet2006b, author = {Jaume Bonet and Gianluigi Caltabiano and Abdul Kareem Khan and Michael A Johnston and Carles Corb\'i and Alex G\'omez and Xavier Rovira and Joan Teyra and Jordi Vill\`a-Freixa}, title = {The role of residue stability in transient protein-protein interactions involved in enzymatic phosphate hydrolysis. A computational study.}, journal = {Proteins}, year = {2006}, volume = {63}, pages = {65--77}, number = {1}, month = {Apr}, abstract = {Finding why protein-protein interactions (PPIs) are so specific can provide a valuable tool in a variety of fields. Statistical surveys of so-called transient complexes (like those relevant for signal transduction mechanisms) have shown a tendency of polar residues to participate in the interaction region. Following this scheme, residues in the unbound partners have to compete between interacting with water or interacting with other residues of the protein. On the other hand, several works have shown that the notion of active site electrostatic preorganization can be used to interpret the high efficiency in enzyme reactions. This preorganization can be related to the instability of the residues important for catalysis. In some enzymes, in addition, conformational changes upon binding to other proteins lead to an increase in the activity of the enzymatic partner. In this article the linear response approximation version of the semimacroscopic protein dipoles Langevin dipoles (PDLD/S-LRA) model is used to evaluate the stability of several residues in two phosphate hydrolysis enzymes upon complexation with their activating partners. In particular, the residues relevant for PPI and for phosphate hydrolysis in the CDK2/Cyclin A and Ras/GAP complexes are analyzed. We find that the evaluation of the stability of residues in these systems can be used to identify not only active site regions but it can also be used as a guide to locate "hot spots" for PPIs. We also show that conformational changes play a major role in positioning interfacing residues in a proper "energetic" orientation, ready to interact with the residues in the partner protein surface. Thus, we extend the preorganization theory to PPIs, extrapolating the results we obtained from the above-mentioned complexes to a more general case. We conclude that the correlation between stability of a residue in the surface and the likelihood that it participates in the interaction can be a general fact for transient PPIs.}, doi = {10.1002/prot.20791}, institution = {Computational Biochemistry and Biophysics Laboratory, Research Group on Biomedical Informatics (GRIB), IMIM/UPF, Barcelona, Spain.}, keywords = { Kinase 2, chemistry; Adenosine Triphosphate, chemistry; Animals; Binding Sites; Computational Biology, methods; Cyclin A, chemistry; Cyclins, chemistry; Enzymes, chemistry; GTP Phosphohydrolases, chemistry; Humans; Hydrolysis; Models, Molecular; Molecular Conformation; Phosphates, chemistry; Protein Binding; Protein Conformation; Protein Interaction Mapping; Proteins, chemistry; Proteomics, methods; Software; Static Electricity; Thermodynamics}, owner = {jordivilla}, pmid = {16374872}, timestamp = {2010.03.14}, url = {http://dx.doi.org/10.1002/prot.20791} }
[2005,article] bibtex

M. A. Johnston, I. F. Galván, and J. Villà-Freixa, "Framework-based design of a new all-purpose molecular simulation application: the Adun simulator.," J Comput Chem, vol. 26, iss. 15, pp. 1647-1659, 2005.

@ARTICLE{Johnston2005b, author = {Michael A Johnston and Ignacio Fdez Galv\'an and Jordi Vill\`a-Freixa}, title = {Framework-based design of a new all-purpose molecular simulation application: the Adun simulator.}, journal = {J Comput Chem}, year = {2005}, volume = {26}, pages = {1647--1659}, number = {15}, month = {Nov}, abstract = {Here we present Adun, a new molecular simulator that represents a paradigm shift in the way scientific programs are developed. The traditional algorithm centric methods of scientific programming can lead to major maintainability and productivity problems when developing large complex programs. These problems have long been recognized by computer scientists; however, the ideas and techniques developed to deal with them have not achieved widespread adoption in the scientific community. Adun is the result of the application of these ideas, including pervasive polymorphism, evolutionary frameworks, and refactoring, to the molecular simulation domain. The simulator itself is underpinned by the Adun Framework, which separates the structure of the program from any underlying algorithms, thus giving a completely reusable design. The aims are twofold. The first is to provide a platform for rapid development and implementation of different simulation types and algorithms. The second is to decrease the learning barrier for new developers by providing a rigorous and well-defined structure. We present some examples on the use of Adun by performing simple free-energy simulations for the adiabatic charging of a single ion, using both free-energy perturbation and the Bennett's method. We also illustrate the power of the design by detailing the ease with which ASEP/MD, an elaborated mean field QM/MM method originally written in FORTRAN 90, was implemented into Adun.}, doi = {10.1002/jcc.20312}, institution = {Computational Biochemistry and Biophysics Laboratory, Research Group on Biomedical Informatics (GRIB), Institut Municipal d'Investigaci� M�dica and Universitat Pompeu Fabra, C/Doctor Aiguader, 80 08003 Barcelona, Catalunya, Spain.}, keywords = {Algorithms; Computer Simulation; Equipment Design; Models, Chemical; Software}, owner = {jordivilla}, pmid = {16175583}, timestamp = {2010.03.14}, url = {http://dx.doi.org/10.1002/jcc.20312} }
[2004,article] bibtex

M. Barbany, H. Gutiérrez-de-Terán, F. Sanz, and J. Villà-Freixa, "Towards a MIP-based alignment and docking in computer-aided drug design.," Proteins, vol. 56, iss. 3, pp. 585-594, 2004.

@ARTICLE{Barbany2004b, author = {Montserrat Barbany and Hugo Guti\'errez-de-Ter\'an and Ferran Sanz and Jordi Vill\`a-Freixa}, title = {Towards a MIP-based alignment and docking in computer-aided drug design.}, journal = {Proteins}, year = {2004}, volume = {56}, pages = {585--594}, number = {3}, month = {Aug}, abstract = {Structural alignment of ligands in their biological conformation is a crucial step in the building of pharmacophoric models in structure-based drug design. In addition, docking algorithms are limited in some cases by the quality of the scoring functions and the limited flexibility of the environment that the different programs allow. On the other hand, GRID molecular interaction potentials (MIPs) have been used for a long time in 3D-QSAR studies. However, in most of these studies the alignment of the molecules is performed on the basis of geometrical or physico-chemical criteria that differ from the MIPs used in the partial least squares statistical analysis. We have previously developed a method to use the same scoring function for the molecular alignment and for 3D-QSAR studies. This methodology, based on the use of GRID potentials, consists in the weighted averaging of similarities of the relevant MIPs of the molecules to be aligned. Here we present a method to obtain the weights for the different GRID probes in the average based on the structural information on protein-ligand complexes for relevant systems. The method, implemented in MIPSIM, is shown to yield good accuracy in the prediction of the alignments for two systems: a set of three inhibitors of dihydrofolate reductase and a set of fifteen non-nucleoside HIV-1 reverse transcriptase inhibitors (NNRTIs). The smooth GRID potentials are shown to capture the flexible character of the active site, as opposed to traditional docking scoring energy functions.}, doi = {10.1002/prot.20153}, institution = {Research Group on Biomedical Informatics (GRIB)-IMIM/UPF, Barcelona, Spain.}, keywords = {Binding Sites; Computer-Aided Design; Drug Design; Folic Acid Antagonists, chemistry/metabolism; HIV Reverse Transcriptase, chemistry/metabolism; Ligands; Models, Chemical; Models, Molecular; Protein Binding, physiology; Protein Conformation; Quantitative Structure-Activity Relationship; Reverse Transcriptase Inhibitors, chemistry/metabolism; Software; Tetrahydrofolate Dehydrogenase, chemistry/metabolism; Thermodynamics}, owner = {jordivilla}, pmid = {15229890}, timestamp = {2010.03.14}, url = {http://dx.doi.org/10.1002/prot.20153} }
[2004,article] bibtex

J. Villà-Freixa, "Book Review: Thermodynamics of Biochemical Reactions. By Robert A. Alberty," ChemPhysChem, vol. 5(2), pp. 287-288, 2004.

@ARTICLE{Villa2004, author = {Jordi Vill\`a-Freixa}, title = {{Book Review: Thermodynamics of Biochemical Reactions. By Robert A. Alberty}}, journal = {ChemPhysChem}, year = {2004}, volume = {5(2)}, pages = {287--288}, doi = {10.1002/cphc.200490010}, url = {http://www3.interscience.wiley.com/journal/107615557/abstract} }
[2003,article] bibtex

N. Centeno, J. Villà-Freixa, and B. Oliva, "Teaching structural bioinformatics at the undergraduate level," Biochem. Mol. Biol. Educ, vol. 31, pp. 386-391, 2003.

@ARTICLE{Centeno2003a, author = {NB Centeno and J Vill{\`a}-Freixa and B Oliva}, title = {Teaching structural bioinformatics at the undergraduate level}, journal = {Biochem. Mol. Biol. Educ}, year = {2003}, volume = {31}, pages = {386--391}, date-added = {2009-11-04 08:23:05 +0100}, date-modified = {2009-11-13 10:06:52 +0100}, local-url = {file://localhost/Users/jvilla/Documents/workspace/jvilla/Papers/2003/Centeno/Biochem.%20Mol.%20Biol.%20Educ%202003%20Centeno.pdf}, owner = {jvilla}, pmid = {16750644762203938140related:XF3smak-dugJ}, rating = {0}, timestamp = {2010.01.03}, url = {http://onlinelibrary.wiley.com/doi/10.1002/bmb.2003.494031060287/pdf} }
[2003,article] bibtex

M. Barbany, H. Gutiérrez-de-Terán, F. Sanz, J. Villà-Freixa, and A. Warshel, "On the generation of catalytic antibodies by transition state analogues," ChemBioChem, vol. 4, iss. 4, pp. 277-85, 2003.

@ARTICLE{Barbany2003, author = {Montserrat Barbany and Hugo Guti{\'e}rrez-de-Ter{\'a}n and Ferran Sanz and Jordi Vill{\`a}-Freixa and Arieh Warshel}, title = {On the generation of catalytic antibodies by transition state analogues}, journal = {ChemBioChem}, year = {2003}, volume = {4}, pages = {277--85}, number = {4}, month = {Apr}, abstract = {The effective design of catalytic antibodies represents a major conceptual and practical challenge. It is implicitly assumed that a proper transition state analogue (TSA) can elicit a catalytic antibody (CA) that will catalyze the given reaction in a similar way to an enzyme that would evolve (or was evolved) to catalyze this reaction. However, in most cases it was found that the TSA used produced CAs with relatively low rate enhancement as compared to the corresponding enzymes, when these exist. The present work explores the origin of this problem, by developing two approaches that examine the similarity of the TSA and the corresponding transition state (TS). These analyses are used to assess the proficiency of the CA generated by the given TSA. Both approaches focus on electrostatic effects that have been found to play a major role in enzymatic reactions. The first method uses molecular interaction potentials to look for the similarity between the TSA and the TS and, in principle, to help in designing new haptens by using 3D quantitative structure-activity relationships. The second and more quantitative approach generates a grid of Langevin dipoles, which are polarized by the TSA, and then uses the grid to bind the TS. Comparison of the resulting binding energy with the binding energy of the TS to the grid that was polarized by the TS provides an estimate of the proficiency of the given CA. Our methods are used in examining the origin of the difference between the catalytic power of the 1F7 CA and chorismate mutase. It is demonstrated that the relatively small changes in charge and structure between the TS and TSA are sufficient to account for the difference in proficiency between the CA and the enzyme. Apparently the environment that was preorganized to stabilize the TSA charge distribution does not provide a sufficient stabilization to the TS. The general implications of our findings and the difficulties in designing a perfect TSA are discussed. Finally, the possible use of our approach in screening for an optimal TSA is pointed out.}, affiliation = {Computational Structural Biology Laboratory, Research Group on Biomedical Informatics (GRIB)-IMIM/UPF Passeig Mar{\'\i}tim de la Barceloneta 37-49 08003 Barcelona, Spain.}, date-added = {2010-03-14 23:10:22 +0100}, date-modified = {2010-03-14 23:26:07 +0100}, doi = {10.1002/cbic.200390048}, keywords = {Drug Stability, Structure-Activity Relationship, Antibodies: Catalytic, Models: Molecular, Chemistry: Physical, Physicochemical Phenomena, Molecular Structure}, language = {eng}, owner = {jordivilla}, pmid = {12672107}, rating = {0}, timestamp = {2010.03.14}, url = {http://onlinelibrary.wiley.com/doi/10.1002/cbic.200390048/pdf} }
[2003,article] bibtex

A. Warshel and J. Villà-Freixa, "Comment on Effect of Active Site Mutation Phe93 Trp in the Horse Liver Alcohol Dehydrogenase Enzyme on Catalysis: A Molecular Dynamics Study"," J. Phys. Chem. B, vol. 107, pp. 12370-12371, 2003.

@ARTICLE{Warshel2003, author = {Warshel, A. and Vill\`a-Freixa, J.}, title = {{Comment on �Effect of Active Site Mutation Phe93 � Trp in the Horse Liver Alcohol Dehydrogenase Enzyme on Catalysis: A Molecular Dynamics Study"}}, journal = {J. Phys. Chem. B}, year = {2003}, volume = {107}, pages = {12370--12371}, url = {http://pubs.acs.org/doi/abs/10.1021/jp034932b} }
[2002,article] bibtex

J. Rodrigo, M. Barbany, H. Gutiérrez-de-Terán, N. B. Centeno, M. de Cáceres, C. Dezi, F. Fontaine, J. J. Lozano, M. Pastor, J. Villà, and F. Sanz, "Comparison of biomolecules on the basis of Molecular Interaction Potentials," J. Braz. Chem. Soc., vol. 13, pp. 795-799, 2002.

@ARTICLE{Rodrigo2002, author = {Rodrigo, J. and Barbany, M. and Guti\'errez-de-Ter\'an, H. and Centeno, N. B. and de C\'aceres, Miquel and Dezi, Cristina and Fontaine, Fabien and Lozano, Juan Jos\'{e} and Pastor, M. and Vill\`a, J. and Sanz, F.}, title = {{Comparison of biomolecules on the basis of Molecular Interaction Potentials}}, journal = {J. Braz. Chem. Soc.}, year = {2002}, volume = {13}, pages = {795-799}, doi = {10.1590/S0103-50532002000600010}, url = {http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532002000600010} }
[2002,article] bibtex

D. G. Truhlar, J. Gao, C. Alhambra, M. Garcia-Viloca, J. Corchado, M. L. Sánchez, and J. Villà, "The incorporation of quantum effects in enzyme kinetics modeling," Accounts of Chemical Research, vol. 35, iss. 6, pp. 341-9, 2002.

@ARTICLE{Truhlar2002, author = {Donald G Truhlar and Jiali Gao and Cristobal Alhambra and Mireia Garcia-Viloca and Jos{\'e} Corchado and Maria Luz S{\'a}nchez and Jordi Vill{\`a}}, title = {The incorporation of quantum effects in enzyme kinetics modeling}, journal = {Accounts of Chemical Research}, year = {2002}, volume = {35}, pages = {341--9}, number = {6}, month = {Jun}, abstract = {We present an overview of new procedures for including quantum mechanical effects in enzyme kinetics. Quantum effects are included in three ways: (1) The electronic structure of the atoms in the catalytic center is treated quantum mechanically in order to calculate a realistic potential energy surface for the bond rearrangement process. (2) The discrete nature of quantum mechanical vibrational energies is incorporated in the treatment of nuclear motion for computing the potential of mean force. (3) Multidimensional tunneling contributions are included. These procedures are illustrated by applications to proton abstractions catalyzed by enolase and methylamine dehydrogenase and hydride-transfer reactions by alcohol dehydrogenase and xylose isomerase.}, affiliation = {Department of Chemistry and Supercomputer Institute, University of Minnesota, 207 Pleasant Street SE, Minneapolis, Minnesota 55455-0431, USA. truhlar@umn.edu}, date-added = {2010-03-14 23:10:38 +0100}, date-modified = {2010-03-14 23:17:30 +0100}, keywords = {Enzymes, Models: Chemical, Catalysis, Quantum Theory, Kinetics, Motion}, language = {eng}, local-url = {file://localhost/Users/jordivilla/Documents/workspace/jvilla/Papers/2002/Truhlar/Accounts%20of%20Chemical%20Research%202002%20Truhlar.pdf}, owner = {jordivilla}, pii = {ar0100226}, pmid = {12069618}, rating = {0}, timestamp = {2010.03.14}, url = {http://www.ncbi.nlm.nih.gov/pubmed/12069618} }
[2002,article] bibtex

A. Shurki, M. Strajbl, J. Villà, and A. Warshel, "How much do enzymes really gain by restraining their reacting fragments?," J Am Chem Soc, vol. 124, iss. 15, pp. 4097-107, 2002.

@ARTICLE{Shurki2002, author = {A Shurki and M Strajbl and J Vill{\`a} and A Warshel}, title = {How much do enzymes really gain by restraining their reacting fragments?}, journal = {J Am Chem Soc}, year = {2002}, volume = {124}, pages = {4097--107}, number = {15}, month = {Apr}, abstract = {The steric effect, exerted by enzymes on their reacting substrates, has been considered as a major factor in enzyme catalysis. In particular, it has been proposed that enzymes catalyze their reactions by pushing their reacting fragments to a catalytic configuration which is sometimes called near attack configuration (NAC). This work uses computer simulation approaches to determine the relative importance of the steric contribution to enzyme catalysis. The steric proposal is expressed in terms of well defined thermodynamic cycles that compare the reaction in the enzyme to the corresponding reaction in water. The S(N)2 reaction of haloalkane dehalogenase from Xanthobacter autotrophicus GJ10, which was used in previous studies to support the strain concept is chosen as a test case for this proposal. The empirical valence bond (EVB) method provides the reaction potential surfaces in our studies. The reliability and efficiency of this method make it possible to obtain stable results for the steric free energy. Two independent strategies are used to evaluate the actual magnitude of the steric effect. The first applies restraints on the substrate coordinates in water in a way that mimics the steric effect of the protein active site. These restraints are then released and the free energy associated with the release process provides the desired estimate of the steric effect. The second approach eliminates the electrostatic interactions between the substrate and the surrounding in the enzyme and in water, and compares the corresponding reaction profiles. The difference between the resulting profiles provides a direct estimate of the nonelectrostatic contribution to catalysis and the corresponding steric effect. It is found that the nonelectrostatic contribution is about -0.7 kcal/mol while the full "apparent steric contribution" is about -2.2 kcal/mol. The apparent steric effect includes about -1.5 kcal/mol electrostatic contribution. The total electrostatic contribution is found to account for almost all the observed catalytic effect ( approximately -6.1 kcal/mol of the -6.8 calculated total catalytic effect). Thus, it is concluded that the steric effect is not the major source of the catalytic power of haloalkane dehalogenase. Furthermore, it is found that the largest component of the apparent steric effect is associated with the solvent reorganization energy. This solvent-induced effect is quite different from the traditional picture of balance between the repulsive interaction of the reactive fragments and the steric force of the protein.}, affiliation = {Department of Chemistry, University of Southern California, Los Angeles, California 90089-1062, USA.}, date-added = {2010-03-14 23:10:38 +0100}, date-modified = {2010-03-14 23:23:22 +0100}, keywords = {Computer Simulation, Catalysis, Models: Chemical, Hydrolases, Thermodynamics, Static Electricity, Water, Protein Conformation}, language = {eng}, local-url = {file://localhost/Users/jordivilla/Documents/workspace/jvilla/Papers/2002/Shurki/J%20Am%20Chem%20Soc%202002%20Shurki.pdf}, owner = {jordivilla}, pii = {ja012230z}, pmid = {11942849}, rating = {0}, timestamp = {2010.03.14}, url = {http://pubs.acs.org/doi/abs/10.1021/ja012230z} }
[2002,article] bibtex

A. Burykin, C. N. Schutz, J. Villà, and A. Warshel, "Simulations of ion current in realistic models of ion channels: the KcsA potassium channel," Proteins, vol. 47, iss. 3, pp. 265-80, 2002.

@ARTICLE{Burykin2002, author = {A Burykin and C N Schutz and J Vill{\`a} and A Warshel}, title = {Simulations of ion current in realistic models of ion channels: the KcsA potassium channel}, journal = {Proteins}, year = {2002}, volume = {47}, pages = {265--80}, number = {3}, month = {May}, abstract = {Realistic studies of ion current in biologic channels present a major challenge for computer simulation approaches. All-atom molecular dynamics simulations involve serious time limitations that prevent their use in direct evaluation of ion current in channels with significant barriers. The alternative use of Brownian dynamics (BD) simulations can provide the current for simplified macroscopic models. However, the time needed for accurate calculations of electrostatic energies can make BD simulations of ion current expensive. The present work develops an approach that overcomes some of the above challenges and allows one to simulate ion currents in models of biologic channels. Our method provides a fast and reliable estimate of the energetics of the system by combining semimacroscopic calculations of the self-energy of each ion and an implicit treatment of the interactions between the ions, as well as the interactions between the ions and the protein-ionizable groups. This treatment involves the use of the semimacroscopic version of the protein dipole Langevin dipole (PDLD/S) model in its linear response approximation (LRA) implementation, which reduces the uncertainties about the value of the protein "dielectric constant." The resulting free energy surface is used to generate the forces for on-the-fly BD simulations of the corresponding ion currents. Our model is examined in a preliminary simulation of the ion current in the KcsA potassium channel. The complete free energy profile for a single ion transport reflects reasonable energetics and captures the effect of the protein-ionized groups. This calculated profile indicates that we are dealing with the channel in its closed state. Reducing the barrier at the gate region allows us to simulate the ion current in a reasonable computational time. Several limiting cases are examined, including those that reproduce the observed current, and the nature of the productive trajectories is considered. The ability to simulate the current in realistic models of ion channels should provide a powerful tool for studies of the biologic function of such systems, including the analysis of the effect of mutations, pH, and electric potentials.}, affiliation = {Department of Chemistry, University of Southern California, Los Angeles, California 90089-1062, USA.}, date-added = {2010-03-14 23:10:29 +0100}, date-modified = {2010-03-14 23:26:22 +0100}, keywords = {Computer Simulation, Electric Conductivity, Potassium Channels, Ion Transport, Models: Molecular, Static Electricity, Bacterial Proteins, Models: Theoretical}, language = {eng}, local-url = {file://localhost/Users/jordivilla/Documents/workspace/jvilla/Papers/2002/Burykin/Proteins%202002%20Burykin.pdf}, owner = {jordivilla}, pii = {10.1002/prot.10106}, pmid = {11948781}, rating = {0}, timestamp = {2010.03.14}, url = {http://www.ncbi.nlm.nih.gov/pubmed/11948781} }
[2001,article] bibtex

A. Warshel, J. Florián, M. v Strajbl, and J. Villà, "Circe Effect versus Enzyme Preorganization: What Can Be Learned from the Structure of the Most Proficient Enzyme," ChemBioChem, vol. 2, pp. 109-11, 2001.

@ARTICLE{Warshel2001, author = {Warshel, A. and Flori\'an, J. and {\v S}trajbl, M. and Vill\`a, J.}, title = {{Circe Effect versus Enzyme Preorganization: What Can Be Learned from the Structure of the Most Proficient Enzyme}}, journal = {ChemBioChem}, year = {2001}, volume = {2}, pages = {109--11}, url = {http://www.ncbi.nlm.nih.gov/pubmed/11828433} }
[2001,article] bibtex

J. Villà and A. Warshel, "Energetics and Dynamics of Enzymatic Reactions," J. Phys. Chem. B, vol. 105, pp. 7887-907, 2001.

@ARTICLE{Villa2001, author = {Vill\`a, J. and Warshel, A.}, title = {{Energetics and Dynamics of Enzymatic Reactions}}, journal = {J. Phys. Chem. B}, year = {2001}, volume = {105}, pages = {7887--907}, owner = {macbook}, timestamp = {2008.08.21}, url = {http://pubs.acs.org/doi/abs/10.1021/jp011048h} }
[2000,article] bibtex

Y. Kim, J. C. Corchado, J. Villà, J. Xing, and D. G. Truhlar, "Multiconfiguration Molecular Mechanics Algorithm for Potential Energy Surafces of Chemical Reactions," J. Chem. Phys., vol. 112, pp. 2718-2735, 2000.

@ARTICLE{Kim2000, author = {Kim, Y. and Corchado, J. C. and Vill\`a, J. and Xing, J. and Truhlar, D. G.}, title = {{Multiconfiguration Molecular Mechanics Algorithm for Potential Energy Surafces of Chemical Reactions}}, journal = {J. Chem. Phys.}, year = {2000}, volume = {112}, pages = {2718-2735}, date-modified = {2007-10-15 11:52:31 +0200}, owner = {macbook}, url = {http://jcp.aip.org/resource/1/jcpsa6/v112/i6/p2718_s1} }
[2000,article] bibtex

J. Villà, M. Strajbl, T. M. Glennon, Y. Y. Sham, Z. T. Chu, and A. Warshel, "How important are entropic contributions to enzyme catalysis?," Proc. Natl. Acad. Sci. USA, vol. 97, iss. 22, pp. 11899-904, 2000.

@ARTICLE{Villa2000, author = {J Vill\`a and M Strajbl and T M Glennon and Y Y Sham and Z T Chu and A Warshel}, title = {How important are entropic contributions to enzyme catalysis?}, journal = {Proc. Natl. Acad. Sci. USA}, year = {2000}, volume = {97}, pages = {11899--904}, number = {22}, month = {Oct}, abstract = {The idea that enzymes accelerate their reactions by entropic effects has played a major role in many prominent proposals about the origin of enzyme catalysis. This idea implies that the binding to an enzyme active site freezes the motion of the reacting fragments and eliminates their entropic contributions, (delta S(cat)(double dagger))', to the activation energy. It is also implied that the binding entropy is equal to the activation entropy, (delta S(w)(double dagger))', of the corresponding solution reaction. It is, however, difficult to examine this idea by experimental approaches. The present paper defines the entropic proposal in a rigorous way and develops a computer simulation approach that determines (delta S(double dagger))'. This approach allows us to evaluate the differences between (delta S(double dagger))' of an enzymatic reaction and of the corresponding reference reaction in solution. Our approach is used in a study of the entropic contribution to the catalytic reaction of subtilisin. It is found that this contribution is much smaller than previously thought. This result is due to the following: (i) Many of the motions that are free in the reactants state of the reference solution reaction are also free at the transition state. (ii) The binding to the enzyme does not completely freeze the motion of the reacting fragments so that (delta S(double dagger))' in the enzymes is not zero. (iii) The binding entropy is not necessarily equal to (delta S(w)(double dagger))'.}, affiliation = {Department of Chemistry, University of Southern California, Los Angeles, CA 90089, USA.}, date-added = {2010-03-14 23:10:39 +0100}, date-modified = {2010-03-14 23:18:08 +0100}, doi = {10.1073/pnas.97.22.11899}, keywords = {Dipeptides, Entropy, Enzymes, Catalysis}, language = {eng}, local-url = {file://localhost/Users/jordivilla/Documents/workspace/jvilla/Papers/2000/Villa/Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20of%20the%20United%20States%20of%20America%202000%20Villa.pdf}, owner = {jordivilla}, pii = {97/22/11899}, pmid = {11050223}, rating = {0}, timestamp = {2010.03.14}, url = {http://www.pnas.org/content/97/22/11899.abstract} }
[2000,article] bibtex

M. Strajbl, Y. Y. Sham, J. Villà, Z. T. Chu, and A. Warshel, "Calculations of Activation Entropies of Chemical Reactions in Solution," J. Phys. Chem. B, vol. 104, pp. 4578-4584, 2000.

@ARTICLE{vStrajbl2000a, author = {Strajbl, M. and Sham, Y. Y. and Vill\`a, J. and Chu, Z. T. and Warshel, A.}, title = {{Calculations of Activation Entropies of Chemical Reactions in Solution}}, journal = {J. Phys. Chem. B}, year = {2000}, volume = {104}, pages = {4578 -4584}, url = {http://pubs.acs.org/doi/abs/10.1021/jp0003095} }
[2000,article] bibtex

A. Warshel, M. Strajbl, J. Villà, and J. Florián, "Remarkable rate enhancement of orotidine 5′-monophosphate decarboxylase is due to transition-state stabilization rather than to ground-state destabilization," Biochemistry, vol. 39, iss. 48, pp. 14728-38, 2000.

@ARTICLE{Warshel2000, author = {A Warshel and M Strajbl and J Vill{\`a} and J Flori{\'a}n}, title = {{Remarkable rate enhancement of orotidine 5'-monophosphate decarboxylase is due to transition-state stabilization rather than to ground-state destabilization}}, journal = {Biochemistry}, year = {2000}, volume = {39}, pages = {14728--38}, number = {48}, month = {Dec}, abstract = {The remarkable rate enhancement of orotidine 5'-phosphate decarboxylase (ODCase) has been attributed to ground-state destabilization (GSD) by desolvation and more recently to GSD by electrostatic stress. Here we reiterate our previous arguments that the GSD mechanisms are not likely to play a major role in enzyme catalysis and analyze quantitatively the origin of the rate enhancement of ODCase. This analysis involves energy considerations and computer simulations. Our energy considerations show that (i) the previously proposed desolvation mechanism is based on an improper reference state; (ii) a nonpolar active site cannot account for the catalytic effect of the enzyme; (iii) the focus on the role of the negatively charged protein residues in the electrostatic stress GSD mechanism overlooks the fact that the positively charged Lys72 strongly stabilizes the substrate; (iv) although the previous calculation of the actual enzymatic reaction correctly reproduced the observed rate enhancement, it could not obtain this rate enhancement from the calculated binding energies (which are the relevant quantities for determining GSD effects); (v) the GSD mechanism is inconsistent with the observed binding energy of the phosphoribosyl part of the substrate; and (vi) the presumably unstable substrate (orotate) can be stabilized, at equilibrium, by accepting a proton from the solvent. Our computer simulation studies involve two set of calculations. First, we study the catalytic reaction by using an empirical valence bond potential surface calibrated by ab initio calculations of the reference solution reaction. This calculation reproduces the observed catalytic effect of the enzyme. Next, we use free-energy perturbation calculations and evaluated the electrostatic contributions to the binding energies of the ground state and transition state (TS). These calculations show that the rate enhancement in ODCase is due to the TS stabilization rather than to GSD. The differences between our own and the previous theoretical analyses stem from both the selection of the reacting system and the treatment of the long-range electrostatic contributions to the binding energy. The reacting system was previously assumed to encompass only the orotate. However, this selection does not allow proper description of the reaction catalyzed by the enzyme (i.e., [Orotate(-) + LysH(+)] if [uracil + Lys + CO(2)]). Therefore, the reacting system should include both orotate and the general acid in the form of the protonated Lys72 protein residue. This selection leads to a simple and consistent interpretation of the catalytic effect where the electrostatic stabilization of the transition state is due to the fact that the two negatively charged aspartic residues are already placed near the reactive lysine so that they do not have to reorganize significantly during the reaction. Interestingly, even calculations with only orotate(-) as the reacting system do not produce sufficient destabilization to account for a GSD mechanism. In summary, we conclude, in agreement with previous workers, that ODCase catalyzes its reaction by electrostatic effects. However, we show that these effects are associated with TS stabilization due to a reduction in the protein-protein reorganization energy and not with protein-substrate destabilization effects.}, affiliation = {Department of Chemistry, University of Southern California, Los Angeles, California 90089-1062, USA.}, date-added = {2010-03-14 23:10:41 +0100}, date-modified = {2010-03-14 23:21:41 +0100}, keywords = {Uridine Monophosphate, Energy Metabolism, Orotidine-5'-Phosphate Decarboxylase, Computer Simulation, Catalysis, Kinetics, Thermodynamics, Catalytic Domain, Models: Chemical}, language = {eng}, local-url = {file://localhost/Users/jordivilla/Documents/workspace/jvilla/Papers/2000/Warshel/Biochemistry%202000%20Warshel.pdf}, owner = {jordivilla}, pii = {bi000987h}, pmid = {11101287}, rating = {0}, timestamp = {2010.03.14}, url = {http://www.ncbi.nlm.nih.gov/pubmed/11101287} }
[2000,article] bibtex

J. Villà, J. Bentzien, A. González-Lafont, J. M. Lluch, J. Bertran, and A. Warshel, "An Effective Way of Modelling Chemical Catalysis: An Empirical Valence Bond Picture of the Role of the Solvent and Catalyst in Alkylation Reactions," J. Comp. Chem., vol. 21, pp. 607-625, 2000.

@ARTICLE{Villa2000a, author = {Vill\`a, J. and Bentzien, J. and Gonz\'{a}lez-Lafont, A. and Lluch, J. M. and Bertran, J. and Warshel, A.}, title = {{An Effective Way of Modelling Chemical Catalysis: An Empirical Valence Bond Picture of the Role of the Solvent and Catalyst in Alkylation Reactions}}, journal = {J. Comp. Chem.}, year = {2000}, volume = {21}, pages = {607-625}, url = {http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1096-987X(200006)21:8%3C607::AID-JCC3%3E3.0.CO;2-R/pdf} }
[2000,article] bibtex

T. M. Glennon, J. Villà, and A. Warshel, "How does GAP catalyze the GTPase reaction of Ras? A computer simulation study," Biochemistry, vol. 39, iss. 32, pp. 9641-51, 2000.

@ARTICLE{Glennon2000, author = {T M Glennon and J Vill{\`a} and A Warshel}, title = {How does GAP catalyze the GTPase reaction of Ras? A computer simulation study}, journal = {Biochemistry}, year = {2000}, volume = {39}, pages = {9641--51}, number = {32}, month = {Aug}, abstract = {The formation of a complex between p21(ras) and GAP accelerates the GTPase reaction of p21(ras) and terminates the signal for cell proliferation. The understanding of this rate acceleration is important for the elucidation of the role of Ras mutants in tumor formation. In principle there are two main options for the origin of the effect of GAP. One is a direct electrostatic interaction between the residues of GAP and the transition state of the Ras-GAP complex and the other is a GAP-induced shift of the structure of Ras to a configuration that increases the stabilization of the transition state. This work examines the relative importance of these options by computer simulations of the catalytic effect of Ras. The simulations use the empirical valence bond (EVB) method to study the GTPase reaction along the alternative associative and dissociative paths. This approach reproduces the trend in the overall experimentally observed catalytic effect of GAP: the calculated effect is 7 +/- 3 kcal/mol as compared to the observed effect of approximately 6.6 kcal/mol. Furthermore, the calculated effect of mutating Arg789 to a nonpolar residue is 3-4 kcal/mol as compared to the observed effect of 4.5 kcal/mol for the Arg789Ala mutation. It is concluded, in agreement with previous proposals, that the effect of Arg789 is associated with its direct interaction with the transition state charge distribution. However, calculations that use the coordinates of Ras from the Ras-GAP complex (referred to here as Ras') reproduce a significant catalytic effect relative to the Ras coordinates. This indicates that part of the effect of GAP involves a stabilization of a catalytic configuration of Ras. This configuration increases the positive electrostatic potential on the beta-phosphate (relative to the corresponding situation in the free Ras). In other words, GAP stabilizes the GDP bound configuration of Ras relative to that of the GTP-bound conformation. The elusive oncogenic effect of mutating Gln61 is also explored. The calculated effect of such mutations in the Ras-GAP complex are found to be small, while the observed effect is very large (8.7 kcal/mol). Since the Ras is locked in its Ras-GAP configuration in our simulations, we conclude that the oncogenic effect of mutation of Gln61 is indirect and is associated most probably with the structural changes of Ras upon forming the Ras-GAP complex. In view of these and the results for the Ras' we conclude that GAP activates Ras by both direct electrostatic stabilization of the transition state and an indirect allosteric effect that stabilizes the GDP-bound form. The present study also explored the feasibility of the associative and dissociative mechanism in the GTPase reaction of Ras. It is concluded that the reaction is most likely to involve an associative mechanism.}, affiliation = {Department of Chemistry, University of Southern California, Los Angeles, California 90089-1062, USA.}, date-added = {2010-03-14 23:10:35 +0100}, date-modified = {2010-03-14 23:24:26 +0100}, keywords = {Models: Chemical, Enzyme Activation, GTPase-Activating Proteins, GTP Phosphohydrolases, Models: Molecular, Computer Simulation, Thermodynamics, Proto-Oncogene Proteins p21(ras), Static Electricity}, language = {eng}, local-url = {file://localhost/Users/jordivilla/Documents/workspace/jvilla/Papers/2000/Glennon/Biochemistry%202000%20Glennon.pdf}, owner = {jordivilla}, pii = {bi000640e}, pmid = {10933780}, rating = {0}, timestamp = {2010.03.14}, url = {http://pubs.acs.org/doi/abs/10.1021/bi000640e} }
[2000,article] bibtex

M. de Cáceres, J. Villà, J. J. Lozano, and F. Sanz, "MIPSIM: similarity analysis of molecular interaction potentials," Bioinformatics, vol. 16, iss. 6, pp. 568-569, 2000.

@ARTICLE{Caceres2000, author = {Miquel de C\'aceres and Jordi Vill\`a and Juan J. Lozano and Ferran Sanz}, title = {{MIPSIM: similarity analysis of molecular interaction potentials}}, journal = {Bioinformatics}, year = {2000}, volume = {16}, pages = {568-569}, number = {6}, abstract = {Summary: MIPSIM is a computational package designed to analyse and compare 3D distributions of molecular interaction potentials (MIP) of series of biomolecules. Availability: MIPSIM software is freely distributed to non-profit academic institutions through its web site: http://www1.imim.es/mipsim. Other organizations must contact the developers. GAMESS (http://www.msg.ameslab.gov/GAMESS/GAMESS.html) and GRID (peter@biop.ox.ac.uk) are external software required to perform some of the MIPSIM computations. They are obtained under conditions similar to MIPSIM's. Contact: mipsim@imim.es}, doi = {10.1093/bioinformatics/16.6.568}, eprint = {http://bioinformatics.oxfordjournals.org/cgi/reprint/16/6/568.pdf}, url = {http://bioinformatics.oxfordjournals.org/cgi/content/abstract/16/6/568} }
[1999,article] bibtex

C. Alhambra, J. Gao, J. C. Corchado, J. Villà, and D. G. Truhlar, "Quantum Mechanical Dynamical Effects in an Enzyme-Catalyzed Proton Transfer Reaction," J. Am. Chem. Soc., vol. 121, pp. 2253-2258, 1999.

@ARTICLE{Alhambra1999, author = {Alhambra, C. and Gao, J. and Corchado, J. C. and Vill\`a, J. and Truhlar, D. G.}, title = {{Quantum Mechanical Dynamical Effects in an Enzyme-Catalyzed Proton Transfer Reaction}}, journal = {J. Am. Chem. Soc.}, year = {1999}, volume = {121}, pages = {2253-2258}, url = {http://pubs.acs.org/doi/abs/10.1021/ja9831655} }
[1999,article] bibtex

J. Villà, J. Corchado, A. Gonzalez-Lafont, J. Lluch, and D. Truhlar, "Variational Transition-State Theory with Optimized Orientation of the Dividing Surface and Semiclassical Tunneling Calculations for Deuterium and Muonium Kinetic Isotope Effects in the Free Radical Association Reaction H + C2H4 -> C2H5," J. Phys. Chem. A, vol. 103, iss. 26, pp. 5061-5074, 1999.

@ARTICLE{Villa1999, author = {J Vill\`a and JC Corchado and A Gonzalez-Lafont and JM Lluch and DG Truhlar}, title = {Variational Transition-State Theory with Optimized Orientation of the Dividing Surface and Semiclassical Tunneling Calculations for Deuterium and Muonium Kinetic Isotope Effects in the Free Radical Association Reaction H + C2H4 -> C2H5}, journal = {J. Phys. Chem. A}, year = {1999}, volume = {103}, pages = {5061--5074}, number = {26}, url = {http://pubs.acs.org/doi/abs/10.1021/jp990970c} }
[1998,article] bibtex

A. Gonzalez-Lafont, J. Villà, J. M. Lluch, J. Bertrán, R. Steckler, and D. G. Truhlar, "Variational transition state theory and tunneling calculations with reorientation of the generalized transition states for methyl cation transfer," J. Phys. Chem. A, vol. 102, pp. 3420-3428, 1998.

@ARTICLE{Gonzalez-Lafont1998, author = {Gonzalez-Lafont, A. and Vill\`a, J. and Lluch, J. M. and Bertr\'an, J. and Steckler, R. and Truhlar, D. G.}, title = {{Variational transition state theory and tunneling calculations with reorientation of the generalized transition states for methyl cation transfer}}, journal = {J. Phys. Chem. A}, year = {1998}, volume = {102}, pages = {3420--3428}, date-modified = {2007-10-15 11:52:38 +0200}, owner = {macbook}, url = {http://pubs.acs.org/doi/abs/10.1021/jp9807672} }
[1998,article] bibtex

J. Villà, J. C. Corchado, A. Gonzalez-Lafont, J. M. Lluch, and D. G. Truhlar, "Explanation of deuterium and muonium kinetic isotope effects for a hydrogen atom addition to an olefin," J. Am. Chem. Soc., vol. 120, pp. 12141-12142, 1998.

@ARTICLE{Villa1998, author = {Vill\`a, J. and Corchado, J.C. and Gonzalez-Lafont, A. and Lluch, J.M. and Truhlar, D. G.}, title = {{Explanation of deuterium and muonium kinetic isotope effects for a hydrogen atom addition to an olefin}}, journal = {J. Am. Chem. Soc.}, year = {1998}, volume = {120}, pages = {12141--12142}, url = {http://pubs.acs.org/doi/abs/10.1021/ja982616i} }
[1998,article] bibtex

J. Villà, A. Gonzalez-Lafont, J. M. Lluch, and D. G. Truhlar, "Entropic effects on the dynamical bottleneck location and tunneling contributions for C2H4+H -> C2H5: Variable scaling of external correlation energy for association reactions," J. Am. Chem. Soc., vol. 120, pp. 5559-5567, 1998.

@ARTICLE{Villa1998a, author = {Vill\`a, J. and Gonzalez-Lafont, A. and Lluch, J.M. and Truhlar, D. G.}, title = {{Entropic effects on the dynamical bottleneck location and tunneling contributions for C2H4+H -> C2H5: Variable scaling of external correlation energy for association reactions}}, journal = {J. Am. Chem. Soc.}, year = {1998}, volume = {120}, pages = {5559--5567}, url = {http://pubs.acs.org/doi/abs/10.1021/ja980131o} }
[1997,article] bibtex

J. Villà and D. G. Truhlar, "Variational Transition State Theory Without the Minimum Energy Path," Theor. Chem. Acc., vol. 1-4, pp. 317-323, 1997.

@ARTICLE{Villa1997a, author = {Vill\`a, J. and Truhlar, D. G.}, title = {{Variational Transition State Theory Without the Minimum Energy Path}}, journal = {Theor. Chem. Acc.}, year = {1997}, volume = {1-4}, pages = {317-323}, url = {http://www.springerlink.com/content/u14x8t607r6qwmkt/} }
[1997,article] bibtex

J. Villà, A. González-Lafont, J. M. Lluch, J. C. Corchado, and J. Espinosa-García, "Understanding the activation energy trends for the C$_2$H$_4$ + OH $\rightarrow$ C$_2$H$_4$OH reaction by using canonical variational transition state theory," J. Chem. Phys., pp. 7266-7274, 1997.

@ARTICLE{Villa1997, author = {Vill\`a, J. and Gonz\'{a}lez-Lafont, A. and Lluch, J. M. and Corchado, J. C. and Espinosa-Garc\'{i}a, J.}, title = {{Understanding the activation energy trends for the C$_2$H$_4$ + OH $\rightarrow$ C$_2$H$_4$OH reaction by using canonical variational transition state theory}}, journal = {J. Chem. Phys.}, year = {1997}, pages = {7266-7274}, url = {http://jcp.aip.org/resource/1/jcpsa6/v107/i18/p7266_s1} }
[1996,article] bibtex

J. Villà, A. González-Lafont, and J. M. Lluch, "On kinetic isotope effects as tools to reveal solvation changes accompanying a proton transfer. A canonical unified statistical theory calculation," J. Phys. Chem., vol. 100, pp. 19389-19397, 1996.

@ARTICLE{Villa1996, author = {Vill\`a, J. and Gonz\'{a}lez-Lafont, A. and Lluch, J. M.}, title = {{On kinetic isotope effects as tools to reveal solvation changes accompanying a proton transfer. A canonical unified statistical theory calculation}}, journal = {J. Phys. Chem.}, year = {1996}, volume = {100}, pages = {19389--19397}, url = {http://pubs.acs.org/doi/abs/10.1021/jp9613192} }
[1996,article] bibtex

J. Villà, A. González-Lafont, J. M. Lluch, and J. Bertran, "On the interpolation of the frequencies of vibrational modes in variational transition state calculations: an adiabatic or diabatic scheme?," Mol. Phys., pp. 633-644, 1996.

@ARTICLE{Villa1996a, author = {Vill\`a, J. and Gonz\'{a}lez-Lafont, A. and Lluch, J. M. and Bertran, J.}, title = {{On the interpolation of the frequencies of vibrational modes in variational transition state calculations: an adiabatic or diabatic scheme?}}, journal = {Mol. Phys.}, year = {1996}, pages = {633--644}, url = {http://www.informaworld.com/smpp/content~db=all~content=a713828497} }

MSc and PhD thesis

[2010,phdthesis] bibtex

A. L. G. de Lomana, "Computational Approaches to the Modelling of Topological and Dynamical Aspects of Biochemical Networks," PhD Thesis , 2010.

@PHDTHESIS{Lopez2010, author = {Adri\'an L\'opez Garc\'ia de Lomana}, title = {{Computational Approaches to the Modelling of Topological and Dynamical Aspects of Biochemical Networks}}, school = {Universitat Pompeu Fabra}, year = {2010}, abstract = {Regulatory mechanisms of cells can be modelled to control and understand cellular biology. Di�ent levels of abstraction are used to describe biological processes. In this work we have used graphs and di�ential equations to model cellular interactions qualitatively and quantitatively. From di�ent organisms, E. coli and S. cerevisiae, we have analysed data available for they complete interaction and activity networks. At the level of interaction, the protein-protein interaction network, the transcriptional regulatory networks and the metabolic network have been studied; for the activity, both gene and protein proles of the whole organism have been examined. From the rich variety of graph measures, one of primer importance is the degree distribution. I have applied statistical analysis tools to such biological networks in order to characterise the degree distribution. In all cases the studied degree distributions have a heavy-tailed shape, but most of them present signicant di�ences from a power-law model according to a statistical test. Moreover, none of the networks could be unequivocally assigned to any of the tested distribution. On the other hand, in a more ne-grained view, I have used di�ential equations to model dynamics of biochemical systems. First, a software tool called ByoDyn has been created from scratch incorporating a fairly complete range of analysis methods. Both deterministic and stochastic simulations can be performed, models can be analysed by means of parameter estimation, sensitivity, identiability analysis, and optimal experimental design. Moreover, a web interface has been created that provides with the possibility interact with the program in a graphical manner, independent of the user conguration, allowing the execution of the program at di�ent computational environments. Finally, we have applied a protocol of optimal experimental design on a multicellular model of embryogenesis.}, url = {http://dl.dropbox.com/u/8542277/web/thesis/main.260710.colour.pdf} }
[2009,phdthesis] bibtex

M. A. Johnston, "Development of a Molecular Simulator and its Application to Conformational Changes in Biomolecules," PhD Thesis , 2009.

@PHDTHESIS{Johnston2009, author = {Johnston, M. A.}, title = {{Development of a Molecular Simulator and its Application to Conformational Changes in Biomolecules}}, school = {Universitat Pompeu Fabra}, year = {2009}, abstract = {This thesis deals with the creation of a new open-source program and API for biomolecular simulation and its subsequent application to biological problems. The program, Adun, focuses on the key areas of biological free-energy calculations, rapid development and high-performance productivity. Methods such as SCAAS, EVB and switched Generalised-Born have been implemented to realise the first aim. The presence of these techniques, along with a multitude of others, verifies Adun's rapid development potential. All these features are united by an advanced graphical user interface which provides novel capabibilities such as inbuilt data management, and distributed datasharing and computation. Adun's ability to tackle biological problems is illustrated with an investigation of Ras dynamics and the development, implementation and testing of a novel method for determining transition paths. In addition to concretely demonstrating Adun's potential these studies also provide insight into the use of dynamic information in elucidating protein function. The current state of the program and the results of the two studies is discussed and indications of future aims and directions given. In addition personal thoughts on the role of computational biologists as developers of applications, for themselves and the wider scientific community, are provided}, url = {http://www.tesisenxarxa.net/TDX-1015109-103730/} }
[2009,mastersthesis] bibtex

T. Gállo Cassarino, " Molecular Dynamics simulations on the Ras protein family: alignment of the essential movements," Master’s Dissertation , 2009.

@MASTERSTHESIS{GalloCassarino2009, author = {G\'allo Cassarino, Tiziano}, title = {{ Molecular Dynamics simulations on the Ras protein family: alignment of the essential movements}}, school = {Internation Bologna Master in Bioinformatics}, year = {2009}, abstract = {High performance computing methods and novel simulation algorithms that have been developed in recent years are transforming molecular simulations into a routine task for the medium throughput analysis of biomolecules. On the other hand, the interest of structural bioinformatics is migrating from mere classification to proper structure function relationships at the protein family levels. We will start by testing the ability of simulator called Adun, to reproduce known facts about the essential movements of Ras proteins as standalone structures or bound to GTPase activating proteins. This will help us rationalizing the differences between common periodic boundary conditions approaches and the spherical boundary approach (based on Warshel's SCAAS method) as implemented in Adun. Next, we will analyze a representative set of the Ras family of proteins both bound and unbound to GAPs. Our interest resides in discovering a relationship between the consensus essential movements of Ras in its different bound states. We hypothesize that the essential movements of the Ras family will guide us to define better structures for protein docking experiments.} }
[2009,phdthesis] bibtex

A. K. Khan, "Electrostatic Analysis of the Ras Active Site," PhD Thesis , 2009.

@PHDTHESIS{Khan2009, author = {Khan, A. K.}, title = {{Electrostatic Analysis of the Ras Active Site}}, school = {Universitat Pompeu Fabra}, year = {2009}, abstract = {The electrostatic preorganization of the active site has been put forward as the general framework of action of enzymes. Thus, enzymes would position "strategic" residues in such a way to be prepared to catalyze reactions by interacting in a stronger way with the transition state, in this way decreasing the activation energy for the catalytic process. It has been proposed that such electrostatic preorientation should be shown by analyzing the electrostatic stability of individual residues in the active site. Ras protein is an essential signalling molecule and functions as a switch in the cell. The structural features of the Ras protein in its active state (ON state) are different than those in its inactive state (OFF state). In this thesis, an exhaustive analysis of the stability of residues in the active and inactive Ras active site is performed.}, url = {http://www.tesisenxarxa.net/TDX-0714109-112338/} }
[2009,mastersthesis] bibtex

P. Rué, "Tau leap methods with extended stability regions for biochemical kinetics," Master’s Dissertation , 2009.

@MASTERSTHESIS{Rue2009, author = {Ru\'e, Pau}, title = {{Tau leap methods with extended stability regions for biochemical kinetics}}, school = {MSc on Bioinformatics for Health Sciences, Universitat Pompeu Fabra}, year = {2009}, abstract = {Systems of biochemical reactions often involve species with small numbers of molecules. Such low levels promote large random differences in the behaviour of the system that may play a critical role in biological processes. Therefore, with increasing computer power, simulating the dynamics of stochastic systems of biochemical reactions has attracted much recent interest. The modelling of individual reactions in biochemical systems involves a large number of stochastic reaction events that can be simulated by Gillespie's stochastic simulation algorithm (SSA). The key quantity in the SSA is the waiting time, $\tau$, whose value inversely depends on the size of the propensities of the different reactions and which needs to be re-evaluated after every firing event. Such a discrete event simulation may be extremely expensive, in particular for stiff systems where $\tau$ can be very short due to the fast kinetics of some of the channel reactions. Several alternative methods have been put forward to increase the integration step size. The so-called $\tau$--leap approach takes a larger step size by allowing all the reactions to fire, from a given distribution, within that step. Although the expected value for the different species in the reactive system is maintained with respect to more precise methods, the variance at steady state can suffer from large errors as $\tau$ grows. The aim of this work is to extend Poisson $\tau$--leap methods to a general class of Runge--Kutta (RK) $\tau$--leap methods. We show that with the proper selection of the Butcher tableau coefficients, the variance of the extended $\tau$--leap can be well--behaved, leading significantly larger step sizes. The benefit of adapting the extended method to the use of RK frameworks is clear in terms of speed of calculation, as the number of evaluations of the Poisson distribution is still one set per time step, as in the original $\tau$--leap method. The current approach paves the way to explore new multiscale methods to simulate (bio)chemical systems.} }
[2009,mastersthesis] bibtex

V. Carapella, "Modelling cardiac tissue using Hybrid Automata," Master’s Dissertation , 2009.

@MASTERSTHESIS{Carapella2009, author = {Carapella, Valentina}, title = {{Modelling cardiac tissue using Hybrid Automata}}, school = {MSc on Bioinformatics, Universitat Pompeu Fabra and University of Bologna}, year = {2009}, abstract = {The aim of the present work is to investigate the modelling of cardiac cell as an hybrid system, a system that exhibits both continuous and discrete dynamic behaviour, by means of Hybrid Automata. A simple two-dimensional lattice of cells is then implemented to simulate Action Potential propagation.} }
[2008,phdthesis] bibtex

A. Nonell-Canals, "QM and QM/MM studies on Organic and Bioinorganic systems," PhD Thesis , 2008.

@PHDTHESIS{Nonell2008, author = {Nonell-Canals, A.}, title = {{QM and QM/MM studies on Organic and Bioinorganic systems}}, school = {Universitat Rovira i Virgili}, year = {2008}, abstract = {he application of computational chemistry has been expanding in recent years, leading to work in a wide variety of �elds. This thesis collects the contributions we have made in the last years through theoretical chemistry in two particular �elds: asymmetric synthesis involving large organic systems, and selenopro- teins. The unifying factor is the use of the same computational methods, DFT and DFT/MM methods, and the focus in problems of experimental interest.}, url = {http://alfons.elmeuportal.cat/docs/tesi.pdf} }
[2008,mastersthesis] bibtex

A. Gómez-Garrido, "Modelling of COPD pathways," Master’s Dissertation , 2008.

@MASTERSTHESIS{Gomez2008, author = {G\'omez-Garrido, A.}, title = {{Modelling of COPD pathways}}, school = {MSc on Bioinformatics for Health Sciences, Universitat Pompeu Fabra}, year = {2008}, abstract = {Exercise capacity and trainning response are limited in chronic obstructive pulmonary disease (COPD). There are evidencies that these limitations are produced due to a nitroso-redox imbalance mainly caused by distorsion in the respiratory chain function and in the central metabolism of the skeletal muscle. In this work we analyse the sensitivity and identifiability of a kinetic model of central metabolism in the context of metabolic changes caused by COPD at this level. First, we refine the parameters of the model using experimental data of healthy sedentary people. We discuss the complexity of this problem due to the noisy and sparse data. Second, theory information is used to represent the amount of information that the experimental data carries about the unknown parameters. These techniques allow the detection of the key components in the model and how one can design new maximal informative experiments. The metabolites fructose-1,6-biphoshpate (FBP), glyceraldehide-3-phosphate (G3P) and inorganic phosphate (Pn) and the enzyme creatine kinase (CK) are showed to be the principal elements in the regulation and behaviour of central metabolism.} }
[2006,phdthesis] bibtex

M. Barbany, "Three-dimensional similarity of molecules with biological interest on the basis of molecular interaction potentials," PhD Thesis , 2006.

@PHDTHESIS{Barbany2006, author = {Barbany, M.}, title = {{Three-dimensional similarity of molecules with biological interest on the basis of molecular interaction potentials}}, school = {Universitat Pompeu Fabra}, year = {2006}, abstract = {One of the most promising areas of biomedical and pharmaceutical research is computer assisted molecular design, which is based on the modelization of the chemical entities responsible of the pharmacological activity and the search of mathematical models describing the relationship between the physicochemical properties and the biological activity of such entities. In general, the success of these techniques depends critically on the quality of the molecular description and, in particular, on the fact that this description should be appropiate to represent the molecular interaction phenomenon that we intend to describe. In this sense, methodologies based on the molecular interaction potential (MIP) offer important advantages with respect to other techniques. MIPs are interactions of the studied molecule with one or several selected chemical entities and they are useful tools for the comparison of series of compounds displaying related biological behaviours. As it will be shown here, structure-activity studies benefit from a detailed comparative analysis of MIP distributions of prospective drugs. This project aims to develop tools for computer assisted molecular design based on the characterization and comparison of MIPs of different compounds. To this end, the molecular similarity program MIPSim (Molecular Interaction Potentials Similarity analysis) (C�aceres et al., 16, 568-569, Bioinformatics, 2000) has been further developed and applied to different biological and pharmacological problems. MIPSim analyzes and compares MIP distributions of series of biomolecules. One of the objectives of MIPSim is to obtain automatic structural alignments of series of biomolecules based on their MIP distributions. This can be used to stablish hypothesis about their relative orientation at the functional site, which is sometimes non-evident when only taking into account structural features. MIPSim can evaluate MIPs by classical or quantum methods, thanks to its interfaces to programs GRID and GAMESS respectively. This thesis includes four scientific studies which demonstrate the applicability of MIP similarity through MIPSim to study molecules of biological interest. MIPSim has been used to study alignments of biomolecules, to explore the electrostatic properties of enzymes and catalytic antibodies, to help in searching MIP-based docking and finally, to perform a 3DQSAR study based on a MIP alignment.}, url = {http://www.tesisenxarxa.net/TDX-0713109-103129/} }
[1998,phdthesis] bibtex

J. Villà–Freixa, "Teoria variacional de l’estat de transició: nous desenvolupaments metodològics i la seva aplicació a sistemes d’interès químic," PhD Thesis , 1998.

@PHDTHESIS{VillaThesis1998, author = {Vill\`a--Freixa, J.}, title = {{Teoria variacional de l'estat de transici\'o: nous desenvolupaments metodol\`ogics i la seva aplicaci\'o a sistemes d'inter\`es qu\'imic}}, school = {Universitat Aut\`onoma de Barcelona}, year = {1998}, url = {http://www.tesisenxarxa.net/TDX-0630109-101249/} }

Book Chapters

[2009,incollection] bibtex

B. Alsina, A. L. García–Lomana, J. Villà–Freixa, and F. Giráldez, "Developmental biology and mathematics: the rules of an embryo," , Giráldez, F. and Herrero, M. A., Eds., Am. Math. Soc. and Real Soc. Mat. Esp, 2009, vol. 492, pp. 1-12.

@INCOLLECTION{Alsina2009, author = {Berta Alsina and Adri\'an L. Garc\'ia--Lomana and Jordi Vill\`a--Freixa and Fernando Gir\'aldez}, title = {Developmental biology and mathematics: the rules of an embryo}, booktitle = {{Mathematics, Developmental Biology and Tumour Growth}}, publisher = {Am. Math. Soc. and Real Soc. Mat. Esp}, year = {2009}, editor = {Fernando Gir\'aldez and Miguel A. Herrero}, volume = {492}, pages = {1--12}, url = {http://books.google.es/books?id=l5FthtzbKMoC&pg=PA1&lpg=PA1&dq=Developmental+biology+and+mathematics:+the+rules+of+an+embryo&source=bl&ots=ut9RM7ou6N&sig=-n3uA72FSU27B4JapNHHJHFqsco&hl=es&ei=MjFxTI3PAp-U4gbMuuneCA&sa=X&oi=book_result&ct=result&resnum=1&ved=0CBwQ6AEwAA#v=onepage&q=Developmental%20biology%20and%20mathematics%3A%20the%20rules%20of%20an%20embryo&f=false} }
[2008,incollection] bibtex

A. Nonell–Canals, J. Villà–Freixa, and F. Maseras, "The Challenge of Metalloproteins: Some Applications," , Ramos, M. J., Ed., Transworld research network: Trivandium, 2008, pp. 61-80.

@INCOLLECTION{NonellBook2008, author = {Alfons Nonell--Canals and Jordi Vill\`a--Freixa and Feliu Maseras}, title = {{The Challenge of Metalloproteins: Some Applications}}, booktitle = {{Computational Proteomics}}, publisher = {Transworld research network: Trivandium}, year = {2008}, editor = {Maria J. Ramos}, pages = {61--80}, abstract = {The computational study of metalloproteins faces specific challenges, but holds the promise of important rewards in the form of understanding original enzymatic behaviors which cannot be approached by the usual experimental procedures. The stregths and limitations of the usual computational approach of studying the reactivity of the metalloprotein with QM or QM/MM studies of its active center are discussed with a detailed description of available results on two particular examples: heme oxygen transporters and B12 cofactors.}, url = {http://www.ressign.com/UserBookDetail.aspx?bkid=727&catid=189#} }
[2007,incollection] bibtex

M. Harvey, G. Giupponi, J. Villà-Freixa, and G. De Fabritiis, "PS3GRID.NET: Building a distributed supercomputer using the PlayStation 3." , 2007.

@INCOLLECTION{Harvey2007, author = {Harvey, M. and Giupponi, G. and Vill\`a-Freixa, J. and De Fabritiis, G.}, title = {PS3GRID.NET: Building a distributed supercomputer using the PlayStation 3}, booktitle = {Distributed and Grid Computing - Science Made Transparent for Everyone. Principles, Applications and Supporting Communities}, year = {2007}, owner = {macbook}, url = {http://www.cs.umsl.edu/~sanjiv/classes/cs6740/presentation/abadi_presentation.pdf} }
[2005,incollection] bibtex

A. Warshel, M. H. M. Olsson, and J. Villà–Freixa, "Computer Simulations of Isotope Effects in Enzyme Catalysis," , A., K. and H.H., L., Eds., London: CRC Press, 2005, pp. 621-644.

@INCOLLECTION{Warshel2005, author = {Arieh Warshel and Matts H. M. Olsson and Jordi Vill\`a--Freixa}, title = {Computer Simulations of Isotope Effects in Enzyme Catalysis}, booktitle = {Isotope effects in chemistry and biology}, publisher = {CRC Press}, year = {2005}, editor = {Kohen A. and Limbach H.H.}, pages = {621--644}, address = {London}, url = {http://www.crcpress.com/product/isbn/9780824724498;jsessionid=+5341thojkuuOlqJyU-LHw**} }
[2002,incollection] bibtex

F. Sanz, M. de Cáceres, and J. Villà, "Similarity analysis of Molecular Interaction Potential Distributions: The MIPSIM software," , Carbó-Dorca, R., Ed., Kluwer Academic, 2002.

@INCOLLECTION{Sanz2002, author = {Sanz, F. and de C\'aceres, M. and Vill\`a, J.}, title = {{Similarity analysis of Molecular Interaction Potential Distributions: The MIPSIM software}}, booktitle = {{The Fundamentals of Molecular Similarity}}, publisher = {Kluwer Academic}, year = {2002}, editor = {Carb\'o-Dorca, R.}, timestamp = {2008.12.02} }
[2002,incollection] bibtex

J. Villà and A. Warshel, "Modeling and analyzing biocatalysis." Wiley Interscience, 2002.

@INCOLLECTION{Villa2002, author = {Vill\`a, J. and Warshel, A.}, title = {{Modeling and analyzing biocatalysis}}, booktitle = {{Encyclopedia of Catalysis}}, publisher = {Wiley Interscience}, year = {2002}, doi = {10.1002/0471227617.eoc048}, timestamp = {2008.12.02}, url = {http://mrw.interscience.wiley.com/emrw/9780471227618/enccat/article/eoc048/current/abstract} }

Other

[2009,misc] bibtex

J. Zheng, S. Zhang, B. J. Lynch, J. Corchado, Y. Chuang, P. L. Fast, W. Hu, Y. Liu, G. C. Lynch, K. A. Nguyen, C. F. Jackels, A. F. Ramos, B. A. Ellingson, V. S. Melissas, J. Villà, I. Rossi, E. L. Coitiño, J. Pu, T. V. Albu, R. Steckler, B. C. Garrett, A. D. Isaacson, and D. G. Truhlar, POLYRATE 2008: Computer Program for the Calculation of Chemical Reaction Rates for PolyatomicsUniversity of Minnesota, 2009.

@MISC{Zheng2008, author = { Jingjing Zheng and Shuxia Zhang and Benjamin J. Lynch and Jos� C. Corchado and Yao-Yuan Chuang and Patton L. Fast and Wei-Ping Hu and Yi-Ping Liu and Gillian C. Lynch and Kiet A. Nguyen and Charles F. Jackels and Antonio Fernandez Ramos and Benjamin A. Ellingson and Vasilios S. Melissas and Jordi Vill\`a and Ivan Rossi and Elena L. Coiti\~no and Jingzhi Pu and Titus V. Albu and Rozeanne Steckler and Bruce C. Garrett and Alan D. Isaacson and Donald G. Truhlar}, title = {{POLYRATE 2008: Computer Program for the Calculation of Chemical Reaction Rates for Polyatomics}}, year = {2009}, publisher = {University of Minnesota}, url = {http://comp.chem.umn.edu/polyrate/} }
[2009,inproceedings] bibtex

D. Maier, P. Krubasik, S. Losko, M. Hernandez, and J. Villà–Freixa, "Knowledge management for systems biology and translational medicine. Experiences from the EU BioBridge project," in Bioinformatics and Biomedicine Workshop, 2009. BIBMW 2009. IEEE International Conference on, 2009, pp. 341-341.

@inproceedings{maier2009knowledge, title={Knowledge management for systems biology and translational medicine. Experiences from the EU BioBridge project}, author={Maier, D. and Krubasik, P. and Losko, S. and Hernandez, M. and Vill\`a--Freixa, J.}, booktitle={Bioinformatics and Biomedicine Workshop, 2009. BIBMW 2009. IEEE International Conference on}, year={2009}, pages={341--341}, organization={IEEE} }
[2009,misc] bibtex

T. V. Albu, O. Tishchenko, J. C. Corchado, Y. Kim, J. Villà, J. Xing, H. Lin, M. Higashi, and D. G. Truhlar, MC-TINKERATE 2008University of Minnesota, 2009.

@MISC{Albu2009, author = {Titus V. Albu and Oksana Tishchenko and Jos\'e C. Corchado and Yongho Kim and Jordi Vill\`a and Jinhua Xing and Hai Lin and Masahiro Higashi and Donald G. Truhlar}, title = {{MC-TINKERATE 2008}}, year = {2009}, publisher = {University of Minnesota}, url = {http://comp.chem.umn.edu/mc-tinkerate/} }
[2008,inproceedings] bibtex

À. Gómez–Garrido, S. Márquez, M. Hernández, V. Selivanov, M. Cascante, J. Villà–Freixa, and S. Kalko, "Integration of transcriptomics data into systems biology modeling in the BioBridge portal," in Schriftenreihe Informatik 26. BIRD08 2nd International Conference on Bioinformatics Research and Development., 2008, pp. 75-81.

@INPROCEEDINGS{GomezProc2008, author = {\`Alex G\'omez--Garrido and Susanna M\'arquez and Miguel Hern\'andez and Vitaly Selivanov and Marta Cascante and Jordi Vill\`a--Freixa and Susana Kalko}, title = {Integration of transcriptomics data into systems biology modeling in the BioBridge portal}, booktitle = {Schriftenreihe Informatik 26. BIRD08 2nd International Conference on Bioinformatics Research and Development.}, year = {2008}, editor = {Josef K�ng, Kristan Schneider, Roland Wagner}, pages = {75--81}, publisher = {Schriftenreihe Informatik 26}, abstract = {Information coming from omics disciplines is currently fragmented, and frequently the lack of appropriate tools for their integration into global models severely limits progress in the understanding of the underlying mechanisms of complex chronic disorders. EC-funded BioBridge project focusses on the creation of systemic dynamical models to link molecular mechanisms to complex diseases. Thus, the BioBridge portal integrates: 1) structured databases (including metabolic pathways affected by complex disorders); 2) tools for the integration of this data into mathematical models; 3) analysis of multilevel data through simulation to improve previous knowledge; 4) interface for the management of computing resources. Here we present the integration of chronic obstructive pulmonary disease (COPD) transcriptomics data (specifically oligonucleotide microarrays from local or public data) into the simulation of a previously reported model for central metabolism. First, fold change (FC) values of contrasts of interest on these datasets were incorporated into the BioXM-based BioBridge database. Quantitative integration of the FC and correlation values is being considered for the modulation and refinement of the set of parameters used in the differential equations of the model.}, isbn = {978-3-85499-422-0}, journal = {Communications in Computer and Information Science} }
[2007,inproceedings] bibtex

M. Charlot, G. de Fabritiis, A. L. García–Lomana, À. Gómez–Garrido, D. Groen, L. Gulyás, A. Hoekstra, M. A. Johnston, G. Kampis, G. Zwart, S. Robinson, M. Strathern, M. Swain, G. Szemes, and J. Villà–Freixa, "The QosCosGrid project: Quasi-opportunistic supercomputing for complex systems simulations. description of a general framework from different types of applications.," in Proceedings of Ibergrid 2007 conference, Santiago de Compostela, 2007.

@INPROCEEDINGS{Charlot2007, author = {Magali Charlot and Gianni de Fabritiis and Adri\'an L. Garc\'ia--Lomana and \`Alex G\'omez--Garrido and Derek Groen and Laszlo Guly\'as and Alfons Hoekstra and Michael A. Johnston and George Kampis and G. Zwart and Steve Robinson and Mark Strathern and Martin Swain and G\'abor Szemes and Jordi Vill\`a--Freixa}, title = { The QosCosGrid project: Quasi-opportunistic supercomputing for complex systems simulations. description of a general framework from different types of applications.}, booktitle = {{Proceedings of Ibergrid 2007 conference}}, year = {2007}, address = {Santiago de Compostela} }
[2006,misc] bibtex

M. Garcia-Viloca, C. Alhambra, J. Corchado, M. L. Sánchez, J. Villà, J. Gao, and D. G. Truhlar, CRATE v 9.0.1: Module of CHARMM that Interfaces it to POLYRATE, 2006.

@misc{garciamodule, author={Garcia-Viloca, M. and Alhambra, C. and Corchado, J. and S{\'a}nchez, M.L. and Vill{\`a}, J. and Gao, J. and Truhlar, D.G.}, title={CRATE v 9.0.1: Module of CHARMM that Interfaces it to POLYRATE}, year={2006} }
[2005,misc] bibtex

M. Barbany, M. de Cáceres, J. J. Lozano, J. Villà, and F. Sanz, MIPSIM: molecular interaction potential similarity analysisIMIM Hospital del Mar, 2005.

@MISC{Barbany2005, author = {Montserrat Barbany and Miquel de C\'aceres and Juan Jos\'e Lozano and Jordi Vill\`a and Ferran Sanz}, title = {MIPSIM: molecular interaction potential similarity analysis}, year = {2005}, publisher = {IMIM Hospital del Mar}, url = {https://sourceforge.net/projects/mipsim/} }
[2003,misc] bibtex

Z. T. Chu, J. Villà-Freixa, M. v Strajbl, C. N. Schutz, A. Shurki, and A. Warshel, MOLARIS version alpha9.06.01University of Southern California, 2003.

@MISC{Chu2003, author = {Chu, Z. T. and Vill\`a-Freixa, J. and {\v S}trajbl, M. and Schutz, C. N. and Shurki, A. and Warshel, A.}, title = {{MOLARIS version alpha9.06.01}}, year = {2003}, date-modified = {2007-10-15 11:52:30 +0200}, owner = {macbook}, publisher = {University of Southern California}, timestamp = {2008.08.14}, url = {http://futura.usc.edu/programs/index.html} }

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