[How do point amino acid substitutions affect the protein structure?]

In order to estimate the influence of point mutations on the protein structure, 552 pairs of structurally aligned proteins with pairwise sequence identities greater than 60% were analyzed. We selected all isolated point mismatches 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 (< 3%) of all observed mutations leads to significant changes in local conformations; (b) observed substitutions, which affect local conformation are more frequently those of similar (high scoring) amino acid pairs rather than the substitutions thought of as "hazardous" (low scoring), although the overall average score of the changing substitutions is still lower than the corresponding average score for the substitutions that leave the structure unchanged.