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Structure-based method for analyzing protein-protein interfaces.

Ying Gao·Renxiao Wang·Luhua Lai
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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.

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AlanineAnimalsAspartic Acid EndopeptidasesBinding SitesChickensComputational BiologyDatabases, ProteinHIV ProteaseHydrogen BondingLigandsModels, MolecularMolecular ConformationMuramidaseMutationProtein BindingProtein ConformationProtein FoldingProtein Interaction MappingProteinsStructural Homology, ProteinStructure-Activity RelationshipThermodynamicsJournal ArticleResearch Support, Non-U.S. Gov't

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Ying Gao, Renxiao Wang, Luhua Lai. 2003-11-22. Structure-based method for analyzing protein-protein interfaces.. https://doi.org/10.1007/s00894-003-0168-3

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