Dissecting contact potentials for proteins: Relative contributions of individual amino acids

Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, USA.
Proteins Structure Function and Bioinformatics (Impact Factor: 2.92). 01/2007; 70(1):119-30. DOI: 10.1002/prot.21538
Source: PubMed

ABSTRACT Knowledge-based contact potentials are routinely used in fold recognition, binding of peptides to proteins, structure prediction, and coarse-grained models to probe protein folding kinetics. The dominant physical forces embodied in the contact potentials are revealed by eigenvalue analysis of the matrices, whose elements describe the strengths of interaction between amino acid side chains. We propose a general method to rank quantitatively the importance of various inter-residue interactions represented in the currently popular pair contact potentials. Eigenvalue analysis and correlation diagrams are used to rank the inter-residue pair interactions with respect to the magnitude of their relative contributions to the contact potentials. The amino acid ranking is shown to be consistent with a mean field approximation that is used to reconstruct the original contact potentials from the most relevant amino acids for several contact potentials. By providing a general, relative ranking score for amino acids, this method permits a detailed, quantitative comparison of various contact interaction schemes. For most contact potentials, between 7 and 9 amino acids of varying chemical character are needed to accurately reconstruct the full matrix. By correlating the identified important amino acid residues in contact potentials and analysis of about 7800 structural domains in the CATH database we predict that it is important to model accurately interactions between small hydrophobic residues. In addition, only potentials that take interactions involving the protein backbone into account can predict dense packing in protein structures.

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Available from: Nicolae-Viorel Buchete, Jul 30, 2015
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