Refinement of the primary hydration shell model for molecular dynamics simulations of large proteins

A realistic representation of water molecules is important in molecular dynamics simulation of proteins. However, the standard method of solvating biomolecules, that is, immersing them in a box of water with periodic boundary conditions, is computationally expensive. The primary hydration shell (PHS) method, developed more than a decade ago and implemented in CHARMM, uses only a thin shell of water around the system of interest, and so greatly reduces the computational cost of simulations. Applying the PHS method, especially to larger proteins, revealed that further optimization and a partial reworking was required and here we present several improvements to its performance. The model is applied to systems with different sizes, and both water and protein behaviors are compared with those observed in standard simulations with periodic boundary conditions and, in some cases, with experimental data. The advantages of the modified PHS method over its original implementation are clearly apparent when it is applied to simulating the 82 kDa protein Malate Synthase G.