Solvent electrostriction-driven peptide folding revealed by quasi-Gaussian entropy theory and molecular dynamics simulation

A quantitative understanding of the complex relationship between microscopic structure and the thermodynamics driving peptide and protein folding is a major goal of biophysical chemistry. Here, we present a methodology comprising the use of an extended quasi-Gaussian entropy theory parametrized using molecular dynamics simulation that provides a complete description of the thermodynamics of peptide conformational states. The strategy is applied to analyze the conformational thermodynamics of MR121-GSGSW, a peptide well characterized in experimental studies. The results demonstrate that the extended state of the peptide possesses the lowest partial molar entropy. The origin of this entropy decrease is found to be in the increase of the density and orientational order of the hydration water molecules around the peptide, induced by the "unfolding". While such a reduction of the configurational entropy is usually associated with the hydrophobic effect, it is here found to be mainly due to the interaction of the solute charges with the solvent, that is, electrostriction.