Flexible Boundaries for Multiresolution Solvation: An Algorithm for Spatial Multiscaling in Molecular Dynamics Simulations

An algorithm is proposed for performing molecular dynamics (MD) simulations of a biomolecular solute represented at atomistic resolution surrounded by a surface layer of atomistic fine-grained (FG) solvent molecules within a bulk represented by coarse-grained (CG) solvent beads. The method, called flexible boundaries for multiresolution solvation (FBMS), is based on: (i) a three-region layering of the solvent around the solute, involving an FG layer surrounded by a mixed FG CG buffer layer, itself surrounded by a bulk CG region; (ii) a definition of the layer boundary that relies on an effective distance to the solute surface and is thus adapted to the shape of the solute as well as adjusts to its conformational changes. The effective surface distance is defined by inverse-nth power averaging over the distances to all non-hydrogen solute atoms, and the layering is enforced by means of half-harmonic distance restraints, attractive for the FG molecules and repulsive for the CG beads. A restraint-free region at intermediate distances enables the formation of the buffer layer, where the FG and CG solvents can mix freely. The algorithm is tested and validated using the GROMOS force field and the associated FG (SPC) and CG (polarizable CGW) water models. The test systems include pure-water systems, where one FG molecule plays the role of a solute, and a deca-alanine peptide with two widely different solute shapes considered, a-helical and fully extended. In particular, as the peptide unfolds, the number of FG molecules required to fill its close-range solvation layer increases, with the additional molecules being provided by the buffer layer. Further validation involves simulations of four proteins in multiresolution FG/CG mixtures. The resulting structural, energetic, and solvation properties are found to be similar to those observed in corresponding pure FG simulations.