The Conformational Stability/Lability of Peptide Fragments in the Sequence Context of Amino Acids

Criteria for evaluating the conformational stability/lability of peptide fragments referred to fragments of protein structures are formulated. Using the proposed criteria, a statistical analysis of tetrapeptide fragments (their conformations and sequences) was performed in a sample of 25  121 protein chain structures from the PDB protein databank. As a result of the analysis, it was shown that tetrapeptide fragments significantly differ in the degree of the conformational stability/lability from the point of view of the proposed statistical criteria. The results of tetrapeptide denaturing molecular dynamics simulations were used as an independent approach to estimate the stability/lability of peptide fragments. A correlation between the estimates of conformational lability obtained on the basis of a statistical analysis of the ensembles of peptide conformations observed in experimentally determined protein structures and the estimates of conformational lability/stability calculated on the basis of molecular dynamics trajectories is demonstrated. Subgroups of more “conformationally stable peptides,” characterized mainly by the α-helical conformation, were obtained. Consensus tetrapeptides characterized by the lowest conformational lability (the highest conformational stability) were determined using complex criteria. Peptides with increased conformational lability were described. Thus, among all combinatorially possible tetrapeptides, the tetrapeptides that are characterized by certainty about their conformational state play a significant role. The relationship between the degree of conformational certainty of the peptide and its involvement in the primary structure of the protein was characterized. It was found that the role of the conformationally stable peptides in the formation of the protein structure was considerable, since they constitute, on average, approximately 10% of the amino-acid sequence. Using real soluble peptides as examples, the possibility of assessing the conformational stability of any preset amino-acid sequence on the basis of the developed criteria of the conformational lability of tetrapeptides was shown.