Residue-Specific Force Field (RSFF2) improves the modeling of conformational behavior of peptides and proteins

Abstract

A recent report of 3 J HNHα scalar coupling constants for hundreds of two-residue peptides has provided an important opportunity to test simulation force fields for proteins. Here, we compare the abilities of three derivatives of the Amber ff99SB force field to reproduce these data. We report molecular dynamics (MD) simulations of 256 two-residue peptides and show that the recently developed residue-specific force field (RSFF2) produces a dramatic improvement in the agreement with experimental 3 J HNHα coupling constants. We further show that RSFF2 also appears to produce a modest improvement in reproducing the 3 J HNHα coupling constants of five model proteins. Perhaps surprisingly, an analysis of neighboring residue effects (NREs) on the 3 J HNHα coupling constants of the two-residue peptides indicates little difference between the force fields abilities to reproduce experimental NREs. We speculate that this might indicate limitations in the force fields descriptions of nonbonded interactions between adjacent side chains or with terminal capping groups.