Studying Solvation of Small Biomolecules via Molecular Dynamics using a Polarizable Force Field

Abstract

Interactions with solvent have been shown to affect the dynamics of small biomolecules. While bulk properties of solvation can be studied via experiments like spectral measurements, understanding the precise impact of solvent interactions on specific motions of biomolecules, and the spatial extent of impact of the biomolecules on the solvent are accessible through simulations. We have used the polarizable AMOEBA molecular mechanics force field to simulate terahertz (THz) spectra of two zwitterionic peptides, glycine and valine in aqueous solution. Ab initio molecular dynamics (AIMD) simulations have been previously used to study these spectra. An analysis method has been previously developed by Marx and co-workers (Sun et. al. JACS 2014) to decompose the THz spectrum into the component motion modes for specific molecules, as well as modes arising from intermolecular interactions, for AIMD simulations. We present here an approach whereby classical MD simulations performed via the AMOEBA forcefield can be analyzed with that mode decomposition method to obtain dynamic modes for the zwitterions. Based on this decomposition, overall we find very good agreement of the AMOEBA classical MD simulations with AIMD. THz spectral assignments and the spectral decomposition of the total spectrum into intramolecular peptide motions and peptide-water cross-correlation modes shows substantial agreement between AMOEBA and AIMD. The unique feature of this approach comes from the good agreement of the peptide-water cross-correlation modes, which involve distortions of the electron density as a result of polarization and hence cannot be captured by fixed charge force fields. This is a promising first step towards future studies for simulating and decomposing the THz observable for larger solutes such as polymers or proteins where AIMD studies are currently intractable.