Zhu Tong, Xiao Xudong, Ji Changge, Zhang John Z H
Center for Laser and Computational Biophysics, State Key Laboratory of Precision Spectroscopy, East China Normal University, Shanghai 200062, China.
Institute of Theoretical and Computational Science, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, China.
J Chem Theory Comput. 2013 Mar 12;9(3):1788-98. doi: 10.1021/ct301091z. Epub 2013 Feb 28.
A quantum calibrated polarizable-charge transfer force field (QPCT) has been proposed to accurately describe the interaction dynamics of zinc-protein complexes. The parameters of the QPCT force field were calibrated by quantum chemistry calculation and capture the polarization and charge transfer effect. QPCTs are validated by molecular dynamic simulation of the hydration shell of the zinc ion, five proteins containing the most common zinc-binding sites (ZnCys2His2, ZnCys3His1, ZnCys4, Zn2Cys6), as well as protein-ligand binding energy in zinc protein MMP3. The calculated results show excellent agreement with the experimental measurement and with results from QM/MM simulation, demonstrating that QPCT is accurate enough to maintain the correct structural integrity of the zinc binding pocket and provide accurate interaction dynamics of the zinc-residue complex. The current approach can also be extended to the study of interaction dynamics of other metal-containing proteins by recalibrating the corresponding parameters to the specific complexes.
一种量子校准的可极化电荷转移力场（QPCT）已被提出，用于精确描述锌-蛋白质复合物的相互作用动力学。QPCT力场的参数通过量子化学计算进行校准，并捕捉极化和电荷转移效应。通过对锌离子水合壳层、五种含有最常见锌结合位点（ZnCys2His2、ZnCys3His1、ZnCys4、Zn2Cys6）的蛋白质以及锌蛋白MMP3中的蛋白质-配体结合能进行分子动力学模拟，对QPCT进行了验证。计算结果与实验测量结果以及QM/MM模拟结果显示出极好的一致性，表明QPCT足够精确，能够维持锌结合口袋的正确结构完整性，并提供锌-残基复合物准确的相互作用动力学。通过针对特定复合物重新校准相应参数，当前方法还可扩展至研究其他含金属蛋白质的相互作用动力学。
