Comparative conformational analysis of peptide libraries
Saul G. Jacchieri
Abstract
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 a-helix, b-sheet,
3_10-helix, reverse turn I and g-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.
Keywords
comparative conformational analysis, peptide libraries, probabilities of
occurrence of structural motifs, sequence and conformational spaces
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