Revisiting Vacuum Simulations Using Modern Classical Protein Force Fields

Abstract

With the recent extensive improvement of classical biomolecular force fields in solution, the performance of these in vacuum simulations remains unclear. In this work, we perform extensive replica exchange molecular dynamics (REMD) to compare the recent modern force fields. Therefore, we investigate the sampling conformations of the force fields and perform quantum mechanical total energy calculations. We found that the treatment of CMAP or dihedral angle functions does not strongly affect the sampling of the force fields in vacuum simulations, but the inter-residue mainchain-side chain interaction may play important roles. In addition, the sampling area in PC space and the radius of gyration versus N-terminus to C-terminus distances are not dominantly the highest in all cases using ff14SB, but are cumulatively the highest across the 9 peptides in this work. This information may help support the development of future universal transferable force fields.