Assessment of biomolecular force fields for molecular dynamics simulations in a protein crystal

Different biomolecular force fields (OPLS-AA, AMBER03, and GROMOS96) in conjunction with SPC, SPC/E and TIP3P water models are assessed for molecular dynamics simulations in a tetragonal lysozyme crystal. The root mean square deviations for the C(a) atoms of lysozymes are about 0.1 to 0.2 nm from OPLS-AA and AMBER03, smaller than 0.4 nm from GROMOS96. All force fields exhibit similar pattern in B-factors, whereas OPLS-AA and AMBER03 accurately reproduce experimental measurements. Despite slight variations, the primary secondary structures are well conserved using different force fields. Water diffusion in the crystal is approximately ten-fold slower than in bulk phase. The directional and average water diffusivities from OPLS-AA and AMBER03 along with SPC/E model match fairly well with experimental data. Compared to GROMOS96, OPLS-AA and AMBER03 predict larger hydrophilic solvent-accessible surface area of lysozyme, more hydrogen bonds between lysozyme and water, and higher percentage of water in hydration shell. SPC, SPC/E and TIP3P water models have similar performance in most energetic and structural properties, but SPC/E outperforms in water diffusion. While all force fields overestimate the mobility and electrical conductivity of NaCl, a combination of OPLS-AA for lysozyme and the Kirkwood-Buff model for ions is superior to others. As attributed to the steric restraints and surface interactions, the mobility and conductivity in the crystal are reduced by one to two orders of magnitude from aqueous solution.