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根据梭曼与AChE体系的对接要求,对CVFF力场中P-F键的参数进行了修改和补充。之后运用新建的力场参数,对梭曼与AChE进行了对接研究,并实现了应用量子化学/分子力学方法ONIOM(B3LYP/6-31G(d)//UFF)对大分子体系的计算研究。分子力学对接研究表明,新参数与原CVFF力场有较好的一致性,可以完全适应于所研究的体系。同时,通过计算得到10个低能量构象,其中两个最低构象的结构与ONIOM计算结果一致,这也表明对于研究大分子与小分子对接等过程特别是构象搜寻方面,CVFF力场仍然可以得到比较合理的结果。但ONIOM计算也显示出分子力场方法在处理受体与底物之间易发生化学反应或有化学反应产生趋势的体系时会产生误差,对强氢键的估计不足将限制其应用范围。
According to the docking requirements of Soman and AChE system, the parameters of P-F key in CVFF field are modified and supplemented. Afterwards, the new force field parameters were used to study the docking of Soman and AChE, and the computational study on the macromolecule system using ONIOM (B3LYP / 6-31G (d) // UFF) was realized. Molecular mechanics docking studies show that the new parameters and the original CVFF force field has a good consistency, can be completely adapted to the system studied. At the same time, 10 low-energy conformations were obtained by calculation. The structures of the two lowest conformations are consistent with those of ONIOM, which also shows that the CVFF force field can still be compared for the study of docking process of macromolecules with small molecules, especially conformational search Reasonable result. However, ONIOM calculations also show that the molecular force field method can produce errors when dealing with a system that is prone to chemical reaction or chemical reaction between the receptor and the substrate. The lack of estimation of strong hydrogen bonds will limit its application range.