Frictional models for stochastic simulations of proteins

As a first step toward a systematic parametrization of friction constants of atoms in proteins, a model in which frictional resistance is placed explicitly on each atom accessible to solvent is used to calculate overall translational and rotational diffusion constants. It is found that these quantities are relatively insensitive to the precise value of the atomic friction constant, as long as the effective hydrodynamic radius of the surface atoms is approximately 1 Å. However, if only protein atoms are included in the calculation, no reasonable range atomic of radii can reproduce the experimental translational diffusion constant to better than 20% for lysozyme and 5% for ribonuclease. When a hydration shell of approximately 70% coverage for lysozyme and 20% for ribonuclease is included, there is quantitative agreement with experimental results. The sensitivity of peptide diffusion to levels of hydration is also investigated; it is found that for glycine, two bound waters are required to provide agreement with experiment. These findings imply that the effects of solvent damping will be underestimated in stochastic simulations of proteins and peptides unless bound waters are taken into account.