Prediction of structural stability of short beta-hairpin peptides by molecular dynamics and knowledge-based...

The structural stability of peptides in solution strongly affects their binding affinities and specificities. Thus, in peptide biotechnology, an increase in the structural stability is often desirable. The present work combines two orthogonal computational techniques, Molecular Dynamics and a knowledge-based potential, for the prediction of structural stability of short peptides (< 20 residues) in solution.

We tested the new approach on four families of short beta-hairpin peptides: TrpZip, MBH, bhpW and EPO, whose structural stabilities have been experimentally measured in previous studies. For all four families, both computational techniques show considerable correlation (r > 0.65) with the experimentally measured stabilities. The consensus of the two techniques shows higher correlation (r > 0.82).

Our results suggest a prediction scheme that can be used to estimate the relative structural stability within a peptide family. We discuss the applicability of this predictive approach for in-silico screening of combinatorial peptide libraries.