Balanced Amino-Acid-Specific Molecular Dynamics Force Field for the Realistic Simulation of Both Folded and Disordered Proteins.

Abstract

Molecular dynamics (MD) simulations provide a unique atomic-level description of the structure and dynamics of proteins, which is essential for the mechanistic understanding of protein interactions and function in living organisms. However, traditional MD force fields that are optimized for folded proteins often generate overly compact structures and incorrect characteristics of intrinsically disordered proteins (IDPs) and protein regions (IDRs), thereby limiting the quantitative insights that can be gained from MD simulations. We introduce the residue-specific protein force field, ff99SBnmr2, which is derived from ff99SBnmr1 by balancing the backbone dihedral angle potentials in a residue-specific manner to quantitatively reproduce dihedral angle distributions from an experimental coil library. The new force field substantially improves the backbone conformational ensembles of disordered proteins, protein regions, and peptides while keeping well-defined protein structures stable and accurate. This balanced new force field should enable a myriad of applications that require quantitative descriptions of IDPs, IDRs, loop dynamics, and folding/unfolding equilibria in the presence and absence of interaction partners.