title: Empirical estimation of the energetic contribution of individual interface residues in structures of protein-protein complexes.
abstract: We report a simple algorithm to scan interfaces in protein-protein complexes for identifying binding 'hot spots'. The change in side-chain solvent accessible area (DeltaASA) of interface residues has been related to change in binding energy due to mutating interface residues to Ala (DeltaDeltaG (X --> ALA)) based on two criteria-hydrogen bonding across the interface and location in the interface core-both of which are major determinants in specific, high-affinity binding. These relationships are used to predict the energetic contribution of individual interface residues. The predictions are tested against 462 experimental X --> ALA mutations from 28 interfaces with an average unsigned error of 1.04 kcal/mol. More than 80% of interface hot spots (with experimental DeltaDeltaG > or = 2 kcal/mol) could be identified as being energetically important. From the experimental values, Asp, Lys, Tyr and Trp are found to contribute most of the binding energy, burying >45 A2 on average. The method described here would be useful to understand and interfere with protein interactions by assessing the energetic importance of individual interface residues.
authors.affiliation: Department of Biochemistry, Bose Institute, P-1/12 CIT Scheme VIIM, Calcutta, 700054, India.
authors.forename: Mainak
authors.initials: M
authors.lastname: Guharoy
authors.forename: Pinak
authors.initials: P
authors.lastname: Chakrabarti
mesh_terms: D000409:Alanine; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping / Q000379:methods*; D012997:Solvents / Q000737:chemistry; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D000596:Amino Acids; D012997:Solvents; D014867:Water; D000409:Alanine