Transferable and Polarizable Coarse Grained Model for Proteins─ProMPT.

Abstract

The application of classical molecular dynamics (MD) simulations at atomic resolution (fine-grained level, FG), to most biomolecular processes, remains limited because of the associated computational complexity of representing all the atoms. This problem is magnified in the presence of protein-based biomolecular systems that have a very large conformational space, and MD simulations with fine-grained resolution have slow dynamics to explore this space. Current transferable coarse grained (CG) force fields in literature are either limited to only peptides with the environment encoded in an implicit form or cannot capture transitions into secondary/tertiary peptide structures from a primary sequence of amino acids. In this work, we present a transferable CG force field with an explicit representation of the environment for accurate simulations with proteins. The force field consists of a set of pseudoatoms representing different chemical groups that can be joined/associated together to create different biomolecular systems. This preserves the transferability of the force field to multiple environments and simulation conditions. We have added electronic polarization that can respond to environmental heterogeneity/fluctuations and couple it to protein's structural transitions. The nonbonded interactions are parametrized with physics-based features such as solvation and partitioning free energies determined by thermodynamic calculations and matched with experiments and/or atomistic simulations. The bonded potentials are inferred from corresponding distributions in nonredundant protein structure databases. We present validations of the CG model with simulations of well-studied aqueous protein systems with specific protein fold types─Trp-cage, Trpzip4, villin, WW-domain, and β-α-β. We also explore the applications of the force field to study aqueous aggregation of Aβ 16-22 peptides.