title: A systematic study of the energetics involved in structural changes upon association and connectivity in protein interaction networks.
abstract: The study of protein binding mechanisms is a major topic of research in structural biology. Here, we implement a combination of metrics to systematically assess the cost of backbone conformational changes that protein domains undergo upon association. Through the analyses of 2090 unique unbound → bound transitions, from over 12,000 structures, we show that two-thirds of these proteins do not suffer significant structural changes upon binding, and could thus fit the lock-and-key model well. Among the remaining proteins, one-third explores the bound conformation in the unbound state (conformational selection model) and, while most transitions are possible from an energetic perspective, a few do require external help to break the thermodynamic barrier (induced fit model). We also analyze the relationship between conformational transitions and protein connectivity, finding that, in general, domains interacting with many partners undergo smaller changes upon association, and are less likely to freely explore larger conformational changes.
authors.affiliation: Institute for Research in Biomedicine, Joint IRB-BSC Program in Computational Biology, c/Baldiri i Reixac 10-12, 08028 Barcelona, Spain.
authors.forename: Amelie
authors.initials: A
authors.lastname: Stein
authors.forename: Manuel
authors.initials: M
authors.lastname: Rueda
authors.forename: Alejandro
authors.initials: A
authors.lastname: Panjkovich
authors.forename: Modesto
authors.initials: M
authors.lastname: Orozco
authors.forename: Patrick
authors.initials: P
authors.lastname: Aloy
mesh_terms: D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D011506:Proteins