A Transferable Explicit-Solvent Polarizable Coarse-Grained Model for Proteins

Current transferrable coarse-grained (CG) force fields 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 transferrable CG forcefield with an explicit representation of the environment for accurate simulations with proteins. The forcefield consists of a set of pseudo-atoms representing different chemical groups, that can be joined/associated together to create different biomolecular systems. This preserves the transferability of the forcefield to multiple environments and simulation conditions. The novelty of this CG model is the addition of electronic polarization that can respond to environmental heterogeneity/fluctuations and couple to protein's structural transitions. We demonstrate the validity of this model with the folding of several benchmark proteins from scratch without adding extra constraints. All the peptides studied can be nicely folded with their signature secondary and tertiary structures at the correct positions. The CG model shows a great potential to aid biomolecular research, particularly the folding-unfolding process in a realistic cell-like crowded heterogeneous environment.