Quantifying Structural and Functional Restraints on Amino Acid Substitutions in Evolution of Proteins

An essay in memory of Oleg Ptitsyn who was a major influence on our thinking about protein structure, folding, and function

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V. Chelliah and T. L. Blundell^*

Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, CB2 1GA, Cambridge, England; E-mail: tom@cryst.bioc.cam.ac.uk

^* To whom correspondence should be addressed.

Received March 3, 2005

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One of Oleg Ptitsyn's most important papers (Shakhnovich, E., Abkevich, V., and Ptitsyn, O. (1996) Nature, 379, 96-98) describes how knowledge of structure and function can be used to understand better the nature of amino acid substitutions in families and superfamilies of proteins. The selective advantages of retaining structure and function during evolution can be expressed as restraints on the amino acid substitutions that are accepted.

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KEY WORDS: substitution tables, local environments, functional restraints, structural restraints

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