Comparative conformational analysis of peptide libraries.

Six computer-based combinatorial libraries, including tetrapeptide sequences (generated with five amino acids) and conformations (generated with five main chain and three side chain rotamers), were obtained and sequence-conformation probabilities were calculated with a molecular and statistical mechanics procedure. The structural motifs alpha-helix, beta-sheet, 3(10)-helix, reverse turn I and gamma-turn were focused in these calculations. It is shown that sequence-conformation-probability surfaces provide a broad view of structural changes accompanying changes in sequence. Numerical indices are defined to enable comparisons between frequencies of occurrence of these structural motifs in peptide libraries and in a database of low sequence identity protein structures. Fine details of sequence-conformation-probability surfaces show the effect of point mutations. Broad comparisons between different regions of these surfaces indicate how to select the occurrence of structural motifs in the combinatorial synthesis of peptide chains.