title: Molecular binding sites are located near the interface of intrinsic dynamics domains (IDDs).
abstract: We provide evidence supporting that protein-protein and protein-ligand docking poses are functions of protein shape and intrinsic dynamics. Over sets of 68 protein-protein complexes and 240 nonhomologous enzymes, we recognize common predispositions for binding sites to have minimal vibrations and angular momenta, while two interacting proteins orient so as to maximize the angle between their rotation/bending axes (>65°). The findings are then used to define quantitative criteria to filter out docking decoys less likely to be the near-native poses; hence, the chances to find near-native hits can be doubled. With the novel approach to partition a protein into "domains" of robust but disparate intrinsic dynamics, 90% of catalytic residues in enzymes can be found within the first 50% of the residues closest to the interface of these dynamics domains. The results suggest an anisotropic rather than isotropic distribution of catalytic residues near the mass centers of enzymes.
authors.affiliation: Department of Chemistry, College of Chemistry and Chemical Engineering, and Key Laboratory for Chemical Biology of Fujian Province, Xiamen University , Xiamen, P. R. China.
authors.forename: Hongchun
authors.initials: H
authors.lastname: Li
authors.forename: Shun
authors.initials: S
authors.lastname: Sakuraba
authors.forename: Aravind
authors.initials: A
authors.lastname: Chandrasekaran
authors.forename: Lee-Wei
authors.initials: LW
authors.lastname: Yang
mesh_terms: D000465:Algorithms; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004798:Enzymes / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D047495:PPAR gamma / Q000737:chemistry*; D011485:Protein Binding; D047490:Retinoid X Receptor alpha / Q000737:chemistry*; D054852:Small Molecule Libraries / Q000737:chemistry*; D012984:Software; D013816:Thermodynamics
chemical_list: D004798:Enzymes; D008024:Ligands; D047495:PPAR gamma; D047490:Retinoid X Receptor alpha; D054852:Small Molecule Libraries