Towards molecular dynamics simulation of large proteins with a hydration shell at constant pressure.

Molecular dynamics simulation of a large protein in explicit water with periodic boundary conditions is extremely demanding in terms of computation time. Consequently, we have sought approximations of the solvent environment that model its important features. Here, we describe our SAPHYR (Shell Approximation for Protein HYdRation) model in which the protein is surrounded by a shell of water molecules maintained at constant pressure. In addition to the usual pairwise interatomic interactions, these water molecules are subjected to forces approximating van der Waals and dipole-dipole interactions with the implicit surrounding bulk solvent. The SAPHYR model is tested for a system of one argon atom in water and for the protein ubiquitin, and then applied to cytochrome P450cam, a protein with over 400 residues. The results demonstrate that structural and dynamic properties of the simulated systems are improved by use of the SAPHYR model, and that this model provides a significant computational saving over simulations with periodic boundary conditions.