Protein Science, Vol 1, Issue 2 216-226, Copyright © 1992 by Cold Spring Harbor Laboratory Press

ARTICLE

Environment-specific amino acid substitution tables: Tertiary templates and prediction of protein folds

J. OVERINGTON, D. DONNELLY, M. S. JOHNSON, A. SALI and T. L. BLUNDELL
ICRF Unit of Structural Molecular Biology, Department of Crystallography, Birkbeck College, University of London, Malet Street, London WCIE 7HX, UK

The local environment of an amino acid in a folded protein determines the acceptability of mutations at that position. In order to characterize and quantify these structural constraints, we have made a comparative analysis of families of homologous proteins. Residues in each structure are classified according to amino acid type, secondary structure, accessibility of the side chain, and existence of hydrogen bonds from the side chain. Analysis of the pattern of observed substitutions as a function of local environment shows that there are distinct patterns, especially for buried polar residues. The substitution data tables are available on diskette with Protein Science. Given the fold of a protein, one is able to predict sequences compatible with the fold (profiles or templates) and potentially to discriminate between a correctly folded and misfolded protein. Conversely, analysis of residue variation across a family of aligned sequences in terms of substitution profiles can allow prediction of secondary structure or tertiary environment.
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