Molecular dynamics study on mobility and dipole ordering of solvent around proteins: effects of periodic-box size and protein charge

Molecular dynamics simulations of a DNA-binding protein in charged and neutral states were done with periodic boundary boxes of different size (the distance from the protein surface to the box boundary is 6–12 Å). The protein conformation in the neutral state was stable even in the smallest box. The solvent self-diffusion coefficient reached a plateau for protein–water distances greater than 10 Å. Long-range solvent-orientational ordering, which may be important for protein–DNA interactions, was observed around the protein for both states. This ordering explains the reason for the difficulty in the free-energy perturbation method for mutations where the sidechain charge changes.