In order to estimate the influence of point mutations upon a protein structure, the analysis of 556 pairs of structurally aligned proteins has been performed. All occurrences of isolated point amino acid mismatches were derived from these alignments. The statistics of local conformational changes corresponding to these mismatches was studied. This study revealed two surprising aspects: (a) only an extremely minor fraction of all observed mutations leads to sufficient changes in local conformations of polypeptide chains; (b) substitutions of similar amino acids affect local conformation as often as substitution thought of as "hazardous". This fact may be explained in terms of distances between codons.

This work was supported by The Russian Human Genome Program.