Biomolecular Force Fields for Lysozyme Crystal: Assessed From Molecular Dynamics Simulations

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 CĄ atoms of lysozymes are about 0.1 ~ 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 ~ two orders of magnitude from aqueous solution.