Journal of Molecular Modeling

, Volume 10, Issue 1, pp 44–54 | Cite as

Structure-based method for analyzing protein–protein interfaces

Original Paper

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 (ΔΔG≥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.

Figure Key interaction grids at the interface between barnase and barstar. Key interaction grid for barnase and barstar are presented in one figure according to their coordinates. In order to distinguish the two proteins, different icons were assigned. Crosses represent key grids for barstar and dots represent key grids for barnase. The four residues in ball and stick are Asp40 in barstar and Arg83, Arg87, His102 in barnase.

Keywords

Protein–protein interaction Interface analysis Hot spot Correlated mutation PP_SITE 

Notes

Acknowledgement

This work has been supported by the Ministry of Science and Technology of China (the 863 High-tech project and the Basic Research Project 2003CB715900), the National Natural Science Foundation of China and The Committee of Science and Technology of Beijing.

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  1. 1.State Key Laboratory of Structural Chemistry for Stable and Unstable Species, College of Chemistry and Molecular EngineeringPeking UniversityBeijingChina
  2. 2.Center for Theoretical BiologyPeking UniversityBeijingChina
  3. 3.Medical Chemistry and Comprehensive Cancer CenterUniversity of MichiganUSA

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