Energetics of beta-turn formation in a mutant peptide YPGDV from influenza hemagglutinin: an MD simulation study

Reverse turns play an important role in protein folding, molecular recognition and in eliciting immune response. While sequence determinants of reverse turns are known, not much is known about their energetics. In this paper we have investigated the thermodynamics of a reverse turn sequence YPGDV, an experimentally well characterized turn sequence, using molecular dynamics simulations performed over a range of temperatures from 280-360 K using GROMACS 4.0.4 software and all atom OPLS-AA/L force field. The change in folding free energy (Delta A(folding)) for the beta-turn formation in YPGDV peptide shows a linear relationship with temperature. We find that the entropy change (Delta S-folding) for the beta-turn formation is close to zero and the internal energy change (Delta U-folding) is a modest -3.8 kJ mol(-1). These thermodynamic quantities are interpreted in terms of intra-molecular (intra-peptide) and inter-molecular (peptide-solvent) hydrogen bonding interactions. Implications for protein folding and peptide immunogenicity are discussed