Key Laboratory of Mesoscopic Chemistry of MOE, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.
J Phys Chem B. 2011 Aug 25;115(33):10154-62. doi: 10.1021/jp203505v. Epub 2011 Aug 4.
Structures and dynamics of a recently designed dizinc metalloprotein (DFsc) (J. Mol. Biol. 2003, 334, 1101) are studied by molecular dynamics simulation using a dynamically adapted polarized force field derived from fragment quantum calculation for protein in solvent. To properly describe the effect of charge transfer and polarization in the present approach, quantum chemistry calculation of the zinc-binding group is periodically performed (on-the-fly) to update the atomic charges of the zinc-binding group during the MD simulation. Comparison of the present result with those obtained from simulations under standard AMBER force field reveals that charge transfer and polarization are critical to maintaining the correct asymmetric metal coordination in the DFsc. Detailed analysis of the result also shows that dynamic fluctuation of the zinc-binding group facilitates solvent interaction with the zinc ions. In particular, the dynamic fluctuation of the zinc-zinc distance is shown to be an important feature of the catalytic function of the di-ion zinc-binding group. Our study demonstrates that the dynamically adapted polarization approach is computationally practical and can be used to study other metalloprotein systems.
采用动态自适应极化力场的分子动力学模拟研究了最近设计的二锌金属蛋白（DFsc）（J. Mol. Biol. 2003, 334, 1101）的结构和动力学。该力场是从溶剂中蛋白质的片段量子计算中推导出来的。为了在本方法中正确描述电荷转移和极化的影响，周期性地进行锌结合基团的量子化学计算（实时），以在 MD 模拟过程中更新锌结合基团的原子电荷。将本结果与在标准 AMBER 力场下模拟得到的结果进行比较，表明电荷转移和极化对于维持 DFsc 中正确的不对称金属配位至关重要。对结果的详细分析还表明，锌结合基团的动态波动促进了溶剂与锌离子的相互作用。特别是，锌-锌距离的动态波动被证明是二价锌结合基团催化功能的一个重要特征。我们的研究表明，动态自适应极化方法在计算上是可行的，可用于研究其他金属蛋白体系。
