title: Efficient Relaxation of Protein-Protein Interfaces by Discrete Molecular Dynamics Simulations.
abstract: Protein-protein interactions are responsible for the transfer of information inside the cell and represent one of the most interesting research fields in structural biology. Unfortunately, after decades of intense research, experimental approaches still have difficulties in providing 3D structures for the hundreds of thousands of interactions formed between the different proteins in a living organism. The use of theoretical approaches like docking aims to complement experimental efforts to represent the structure of the protein interactome. However, we cannot ignore that current methods have limitations due to problems of sampling of the protein-protein conformational space and the lack of accuracy of available force fields. Cases that are especially difficult for prediction are those in which complex formation implies a non-negligible change in the conformation of the interacting proteins, i.e., those cases where protein flexibility plays a key role in protein-protein docking. In this work, we present a new approach to treat flexibility in docking by global structural relaxation based on ultrafast discrete molecular dynamics. On a standard benchmark of protein complexes, the method provides a general improvement over the results obtained by rigid docking. The method is especially efficient in cases with large conformational changes upon binding, in which structure relaxation with discrete molecular dynamics leads to a predictive success rate double that obtained with state-of-the-art rigid-body docking.
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Baldiri i Reixac 10, Barcelona 08028, Spain.|Joint BSC-IRB Research Program in Computational Biology, Barcelona, Spain.
authors.forename: Agusti
authors.initials: A
authors.lastname: Emperador
authors.affiliation: Barcelona Supercomputing Center, Jordi Girona 29, Barcelona 08034, Spain.|Joint BSC-IRB Research Program in Computational Biology, Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Solernou
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Baldiri i Reixac 10, Barcelona 08028, Spain.|Joint BSC-IRB Research Program in Computational Biology, Barcelona, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Sfriso
authors.affiliation: Barcelona Supercomputing Center, Jordi Girona 29, Barcelona 08034, Spain.|Joint BSC-IRB Research Program in Computational Biology, Barcelona, Spain.
authors.forename: Carles
authors.initials: C
authors.lastname: Pons
authors.affiliation: Barcelona Supercomputing Center, Jordi Girona 29, Barcelona 08034, Spain.|Joint BSC-IRB Research Program in Computational Biology, Barcelona, Spain.|Departament de Bioquímica, Facultat de Biologia, Avgda Diagonal 645, Barcelona 08028, Spain.
authors.forename: Josep Lluis
authors.initials: JL
authors.lastname: Gelpi
authors.affiliation: Barcelona Supercomputing Center, Jordi Girona 29, Barcelona 08034, Spain.|Joint BSC-IRB Research Program in Computational Biology, Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Fernandez-Recio
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Baldiri i Reixac 10, Barcelona 08028, Spain.|Barcelona Supercomputing Center, Jordi Girona 29, Barcelona 08034, Spain.|Joint BSC-IRB Research Program in Computational Biology, Barcelona, Spain.|Departament de Bioquímica, Facultat de Biologia, Avgda Diagonal 645, Barcelona 08028, Spain.
authors.forename: Modesto
authors.initials: M
authors.lastname: Orozco