Multiscale Simulation of Protein Hydration Using the SWINGER Dynamical Clustering Algorithm.

To perform computationally efficient concurrent multiscale simulations of biological macromolecules in solution, where the all-atom (AT) models are coupled to supramolecular coarse-grained (SCG) solvent models, previous studies resorted to modified AT water models, such as the bundled-simple point charge (SPC) models, that use semiharmonic springs to restrict the relative movement of water molecules within a cluster. Those models can have a significant impact on the simulated biomolecules and can lead, for example, to a partial unfolding of a protein. In this work, we employ the recently developed alternative approach with a dynamical clustering algorithm, SWINGER, which enables a direct coupling of original unmodified AT and SCG water models. We perform an adaptive resolution molecular dynamics simulation of a Trp-Cage miniprotein in multiscale water, where the standard SPC water model is interfaced with the widely used MARTINI SCG model, and demonstrate that, compared to the corresponding full-blown AT simulations, the structural and dynamic properties of the solvated protein and surrounding solvent are well reproduced by our approach.