Efficient approximate all-atom solvent accessible surface area method parameterized for folded and denatured protein...

Continuing advances in computer hardware and software are permitting atomic-resolution molecular simulations for longer time scales and on larger systems. Despite these advances, routinely performing atomistic simulations with explicit water for even small proteins, which reach the folding time of such proteins, remains intractable for the foreseeable future. An implicit approximation of the solvent environment using a solvent accessible surface area (SASA) term in a molecular mechanics potential function allows exclusion of the explicit water molecules in protein simulations. This reduces the number of particles by approximately an order of magnitude. We present a fast and acceptably accurate approximate all-atom SASA method parameterized using a set of folded and heat-denatured conformations of globular proteins. The parameters are shown to be transferable to folded and heat-denatured conformations for another set of proteins. Calculation of the approximate SASA and the associated derivatives with respect to atomic positions for a 4644 atom protein requires only 1/11th the CPU time required for calculation of the nonbonded interactions for this system. On a per atom basis, this algorithm is three times faster than the fastest previously published approximate SASA method and achieves the same level of accuracy.