Solvent shell hydration model

Because most biological processes occur in aqueous solvents, MD simulations typically account for the effects of solvation on the biomolecule of interest either explicitly or implicitly.  While fully-implicit solvation models can greatly accelerate MD simulations because they remove individual solvent molecules completely, they cannot be used if the process under study involves interfacial or buried solvent molecules, such as enzyme catalysis.

A compromise between the accuracy of explicit solvent and the speed of implicit solvent is achieved by hybrid models, in which solvent in the vicinity of a macromolecule is represented explicitly, and the effects of the remaining (bulk) solvent on the solute are treated implicitly.

We have developed, implemented and evaluated a hydration shell solvation model, and applied it to microsecond MD simulations of protein systems of various sizes. The model produces simulation statistics that are comparable to those obtained in fully-explicit solvent in a periodic box at a reduced simulation cost. In particular, protein stability, as measured by RMSD from the initial structure, residue fluctuations, and potentials of mean force (PMFs) of conformational change in the solvated alanine dipeptide, as well as PMFs of antibody-antigen separation, correspond well to fully-explicit results. The present simulations support earlier results that found that in cluding only the first 1-2 solvation shells could suffice to capture the essential configurational dynamics of solvated biomolecules.

We have recently extended the model to include curvature dependence parametrized from explicit water simulations, which is expected to reduce artifacts such as high pressure and surface tension.  A manuscript describing the results is in preparation.

Reference:

V. Ovchinnikov, S. Conti, E.Y. Lau, F.C. Lightstone, and M. Karplus. Microsecond molecular dynamics simulations of proteins using a quasi-equilibrium solvation shell model. J. Chem. Theor. Comput., 16(3):1866–1881, 2020.