Riccardi Demian, Li Guohui, Cui Qiang
Department of Chemistry and Theoretical Chemistry Institute, University of Wisconsin, Madison, 1101 University Ave, Madison, Wisconsin 53706.
J Phys Chem B. 2004 May 20;108(20):6467-78. doi: 10.1021/jp037992q.
The importance of accurately treating van der Waals interactions between the quantum mechanical (QM) and molecular mechanical (MM) atoms in hybrid QM/MM simulations has been investigated systematically. First, a set of van der Waals (vdW) parameters was optimized for an approximate density functional method, the self-consistent charge-tight binding density functional (SCC-DFTB) approach, based on small hydrogen-bonding clusters. The sensitivity of condensed phase observables to the SCC-DFTB vdW parameters was then quantitatively investigated by SCC-DFTB/MM simulations of several model systems using the optimized set and two sets of extreme vdW parameters selected from the CHARMM22 forcefield. The model systems include a model FAD molecule in solution and a solvated enediolate, and the properties studied include the radial distribution functions of water molecules around the solute (model FAD and enediolate), the reduction potential of the model FAD and the potential of mean force for an intramolecular proton transfer in the enediolate. Although there are noticeable differences between parameter sets for gas-phase clusters and solvent structures around the solute, thermodynamic quantities in the condensed phase (e.g., reduction potential and potential of mean force) were found to be less sensitive to the numerical values of vdW parameters. The differences between SCC-DFTB/MM results with the three vdW parameter sets for SCC-DFTB atoms were explained in terms of the effects of the parameter set on solvation. The current study has made it clear that efforts in improving the reliability of QM/MM methods for energetical properties in the condensed phase should focus on components other than van der Waals interactions between QM and MM atoms.
在混合量子力学/分子力学（QM/MM）模拟中，准确处理量子力学（QM）和分子力学（MM）原子之间范德华相互作用的重要性已得到系统研究。首先，基于小氢键簇，为一种近似密度泛函方法——自洽电荷紧密束缚密度泛函（SCC-DFTB）方法优化了一组范德华（vdW）参数。然后，通过使用优化集以及从CHARMM22力场中选取的两组极端vdW参数，对几个模型系统进行SCC-DFTB/MM模拟，定量研究凝聚相可观测量对SCC-DFTB vdW参数的敏感性。模型系统包括溶液中的模型FAD分子和溶剂化的烯二醇盐，所研究的性质包括溶质（模型FAD和烯二醇盐）周围水分子的径向分布函数、模型FAD的还原电位以及烯二醇盐中分子内质子转移的平均力势。尽管气相簇的参数集与溶质周围溶剂结构之间存在显著差异，但发现凝聚相中的热力学量（如还原电位和平均力势）对vdW参数的数值不太敏感。根据参数集对溶剂化的影响，解释了SCC-DFTB原子的三种vdW参数集的SCC-DFTB/MM结果之间的差异。当前研究明确表明，提高凝聚相能量性质的QM/MM方法可靠性的努力应集中在除QM和MM原子之间范德华相互作用之外的其他组件上。
