On the vibrational free energy of hydrated proteins

TL;DR

This paper investigates how hydration affects the vibrational free energy of proteins, revealing correlations with conformer rigidity and implications for protein structure prediction.

Contribution

It demonstrates the impact of hydration shells on vibrational free energy and potential energy correlations, highlighting the importance of explicit water modeling in protein conformer analysis.

Findings

Hydration shells induce anti-correlation between free energy and potential energy.

Well-hydrated conformers tend to be more rigid.

Including explicit water molecules can improve conformer discrimination.

Abstract

When the hydration shell of a protein is filled with at least 0.6 gram of water per gram of protein, a significant anti-correlation between the vibrational free energy and the potential energy of energy-minimized conformers is observed. This means that low potential energy, well-hydrated, protein conformers tend to be more rigid than high-energy ones. On the other hand, in the case of CASP target 624, when its hydration shell is filled, a significant average energy gap is observed between the crystal structure and the best conformers proposed during the prediction experiment, strongly suggesting that including explicit water molecules may help identifying unlikely conformers among good-looking ones.