title: Structure-based method for analyzing protein-protein interfaces.
abstract: Hydrogen bond, hydrophobic and vdW interactions are the three major non-covalent interactions at protein-protein interfaces. We have developed a method that uses only these properties to describe interactions between proteins, which can qualitatively estimate the individual contribution of each interfacial residue to the binding and gives the results in a graphic display way. This method has been applied to analyze alanine mutation data at protein-protein interfaces. A dataset containing 13 protein-protein complexes with 250 alanine mutations of interfacial residues has been tested. For the 75 hot-spot residues (deltadelta G > or = 1.5 kcal mol(-1)), 66 can be predicted correctly with a success rate of 88%. In order to test the tolerance of this method to conformational changes upon binding, we utilize a set of 26 complexes with one or both of their components available in the unbound form. The difference of key residues exported by the program is 11% between the results using complexed proteins and those from unbound ones. As this method gives the characteristics of the binding partner for a particular protein, in-depth studies on protein-protein recognition can be carried out. Furthermore, this method can be used to compare the difference between protein-protein interactions and look for correlated mutation.
authors.affiliation: State Key Laboratory of Structural Chemistry for Stable and Unstable Species, College of Chemistry and Molecular Engineering, Peking University, 100871 Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.forename: Renxiao
authors.initials: R
authors.lastname: Wang
authors.forename: Luhua
authors.initials: L
authors.lastname: Lai
mesh_terms: D000409:Alanine / Q000737:chemistry; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry; D001665:Binding Sites; D002645:Chickens; D019295:Computational Biology; D030562:Databases, Protein; D016333:HIV Protease; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D009113:Muramidase / Q000737:chemistry; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D025941:Protein Interaction Mapping; D011506:Proteins / Q000737:chemistry*; D040681:Structural Homology, Protein; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D008024:Ligands; D011506:Proteins; C421864:hen egg lysozyme; D009113:Muramidase; D016282:Aspartic Acid Endopeptidases; D016333:HIV Protease; C065184:p16 protease, Human immunodeficiency virus 2; D000409:Alanine