Understanding Molecular Recognition: A Dissection of Specific and Non-specific Protein-Protein Interfaces.

Ranjit P. Bahadur[1], Pinak Chakrabarti[1], Francis Rodier[2] and Joël Janin[2]
[1] Department of Biochemistry, Bose Institute, P-1/12 CIT Scheme VIIM, Calcutta 700 054, India
[2] Laboratoire d'Enzymologie et de Biochimie Structurales,
CNRS UPR 9063, 91198-Gif-sur-Yvette, France
 

Molecular recognition results from the specific interactions between two molecules. Many biological processes occurring in living cells are carried out or regulated by the specific molecular recognition. We have analyzed known protein structures and developed some parameters that describe the physico-chemical features of the interfaces and which can distinguish between specific and non-specific interactions. Specific interactions are illustrated by 70 protein-protein complexes and by subunit contacts in 122 homodimeric proteins. Non-specific interactions are illustrated by 188 pairs of monomeric proteins making crystal-packing contacts, out of which 103 pairs have 2-fold symmetry and form "crystal dimers" and the rest do not possess such symmetry. Non-specific interfaces are less hydrophobic than in homodimers and contain much fewer fully buried atoms. However, the specific interfaces form clusters of residues which can be further dissected as belonging to core and rim regions depending upon the burial of interface atoms. Non-specific interfaces do not show any of these properties. To assess the differences between specific and non-specific interfaces we develop residue propensity score and hydrophobic interaction score from chemical and amino acid composition in the interfaces. We derive indices to evaluate the atomic packing, which indicate the less compact nature of the non-specific interfaces. We test the potential of all these parameters to identify the homodimeric proteins in crystal structures. A combination of non-polar interface area, the fraction of fully buried interface atoms and residue propensity score can assign the correct quaternary structure at 93-95% level.
 

References
1. A dissection of specific and non-specific protein-protein interfaces. Ranjit Prasad Bahadur, P. Chakrabarti, F. Rodier and J. Janin. J. Mol. Biol. 336, 943-955 (2004).
2. Dissecting Subunit Interfaces in Homodimeric Proteins. Ranjit Prasad Bahadur, Pinak   Chakrabarti, Francis Rodier & Joël Janin.  Proteins, 53, 708-719 (2003).
3 Dissecting protein-protein recognition sites. P. Chakrabarti and J. Janin, Proteins, 47, 334-343 (2002).