A transferable, explicit-solvent polarizable coarse-grained model for proteins

The application of classical molecular dynamics (MD) simulations at atomic resolution, to the majority of biomolecular processes, remains limited because of associated computational complexity. Lowering the level of biomolecule’s spatial representation to a coarse-grained (CG) form by locally averaging atomic positions can provide the necessary computational speed-up to explore biomolecule’s conformational landscape. Current transferrable CG forcefields in literature are either limited to only proteins with the environment encoded in an implicit form (cannot study environmental heterogeneity) or cannot capture transitions into secondary/tertiary protein 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 simulations with proteins. Electronic polarization has been incorporated into the forcefield by augmenting the protein model with auxiliary charges, which can react to environmental stimuli. The non-bonded pair potentials were parametrized with solvation, vaporization, and partitioning free energies of equivalent chemical species. We also present validations of our CG forcefield with simulations of multiple well-studied protein systems.