Structural Effects of an Atomic-Level Layer of Water Molecules around Proteins Solvated in Supra-Molecular Coarse-Grained Water

Atomistic molecular dynamics simulations of proteins in aqueous solution are still limited to the multinanosecond time scale and multinanometer range by computational cost. Combining atomic solutes with a supra-molecular solvent model in hybrid fine-grained/coarse-grained (FG/CG) simulations allows atomic detail in the region of interest while being computationally more efficient. A recent comparison of the properties of four proteins in CG water versus FG water showed the preservation of the secondary and tertiary structure with a computational speed-up of at least an order of magnitude. However, an increased occurrence of hydrogen bonds between side chains was observed due to a lack of hydrogen-bonding partners in the supra-molecular solvent. Here, the introduction of a FG water layer around the protein to recover the hydrogen-bonding pattern of the atomistic simulations is studied. Three layer thicknesses of 0.2, 0.4, and 0.8 nm are considered. A layer thickness of 0.8 nm is found sufficient to recover the behavior of the proteins in the atomistic simulations, whereas the hybrid simulation is still three times more efficient than the atomistic one and the cutoff radius for nonbonded interactions could be increased from 1.4 to 2.0 nm