Molecular Dynamics Simulation of Protein Crystal with Polarized Protein-Specific Charge

Abstract

The polarized force field model is indispensable in the simulation of protein crystal due to the particular electrostatic environment which is different from water solution or membrane. The polarized protein-specific charge (PPC) is fitted from in situ linear scaling quantum mechanical calculations of protein. The atomic charge for each residue is determined by its conformation and its location in the protein. Therefore, it gives a more accurate delineation of charge distribution in protein than the mean-field charge schemes in pairwise force fields do. Two 250 ns molecular simulations are carried out to study the structure and dynamics of crystal toxin protein II from the scorpion Androctonus australis Hector employing PPC, as well as the standard AMBER99SB force field, to investigate the effect of electrostatic polarization on the simulated crystal stability. Results show that PPC provides more reliable description of the monomers in the unit cell as well as the lattice in supercell with much smaller RMSDs and more realistic lattice atomic fluctuations. Most of the interactions at the interfaces among the protein units in the X-ray structure are well preserved, underscoring the important effect of polarization on maintaining the crystal stability.