新型多苯并咪唑环芳识别氨基酸甲酯的分子动力学和密度泛函研究

Exploration of the Molecular Recognition of a Novel Multi-Benzimidazole Cyclophane for a Series of Amino Acid Methyl Esters by Employing Molecular Dynamics and DFT Methods

采用Gaussian 03在B3LYP/6-31G(d)水平上分别优化新型多苯并咪唑环芳(MBICP)受体和氨基酸甲酯(AAME)配体,再用基于模拟退火的分子动力学方法 CDOCKER将配体与受体对接,对每一个复合物获得了一组最低能量的初始构象。最后用Turbomole在BLYP/def-TZVP水平对初始构象进一步优化,并对收敛后的复合物最低能量构象作NBO分析。以密度泛函理论计算获得的相互作用能作为核心参数,采用组合策略建立了表达MBICP-AAME复合物结合常数的定量关系模型,计算了该类复合物的结合常数。对MBICP受体和AAME配体间的作用模式以及影响MBICP受体识别AAME配体的主要因素,作了深入讨论。

The structures of a novel multi-benzimidazole cyclophane（MBICP） acceptor and a series of amino acid methyl ester （AAME） ligands were optimized using Gaussian 03 at the B3LYP/6-31G（d） level, followed by the docking of these ligands to the acceptor by employing CDDOCKER, a CHARMM-based molecular dynamics docking program, to get the initial conformations of the MBICP-AAME complexes. These conformations were further optimized by the aid of Turbomole and analyzed with NBO method at BLYP/def-TZVP level. On the proposed combination strategy which needed the input of binding energies and electron population from the above DFr computation, the authors established a quantitative relationship model that reliably predicted the binding constants of the complexes. The molecular recognition and the nature of the interaction between the MBICP acceptor and AAMEs ligands were also elucidated with this model.