title: Interplay between binding affinity and kinetics in protein-protein interactions.
abstract: To clarify the interplay between the binding affinity and kinetics of protein-protein interactions, and the possible role of intrinsically disordered proteins in such interactions, molecular simulations were carried out on 20 protein complexes. With bias potential and reweighting techniques, the free energy profiles were obtained under physiological affinities, which showed that the bound-state valley is deep with a barrier height of 12 - 33 RT. From the dependence of the affinity on interface interactions, the entropic contribution to the binding affinity is approximated to be proportional to the interface area. The extracted dissociation rates based on the Arrhenius law correlate reasonably well with the experimental values (Pearson correlation coefficient R = 0.79). For each protein complex, a linear free energy relationship between binding affinity and the dissociation rate was confirmed, but the distribution of the slopes for intrinsically disordered proteins showed no essential difference with that observed for ordered proteins. A comparison with protein folding was also performed. Proteins 2016; 84:920-933. © 2016 Wiley Periodicals, Inc.
authors.affiliation: College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.|Center for Quantitative Biology, and Beijing National Laboratory for Molecular Sciences (BNLMS), Peking University, Beijing, 100871, China.
authors.forename: Huaiqing
authors.initials: H
authors.lastname: Cao
authors.affiliation: Institute of Theoretical Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan, 250100, China.
authors.forename: Yongqi
authors.initials: Y
authors.lastname: Huang
authors.affiliation: College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.|Center for Quantitative Biology, and Beijing National Laboratory for Molecular Sciences (BNLMS), Peking University, Beijing, 100871, China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D017510:Protein Folding; D060066:Protein Interaction Maps; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D064267:Intrinsically Disordered Proteins; D011506:Proteins
keywords: binding affinity; coarse-grained model; intrinsically disordered proteins; linear free-energy relationship; protein−protein interaction