中文摘要：

通过生物信息学分析、分子动力学模拟及量子化学计算,对21种邻对位取代酚类模式底物与漆酶的结合能力以及反应活性进行了探讨.生物信息学结构比对分析发现漆酶的活性口袋含有 Asp/Glu206, Asn/His208, Asn264, Gly392和His458等保守的氨基酸残基（氨基酸残基编号以Trametes versicolor漆酶为例, PDB：1KYA）；采用MM-GBSA方法计算了21种酚类模式底物与T. versicolor漆酶的结合自由能.分子力学计算结果表明,漆酶与底物的结合力主要来自Asp206和Asn264等残基与底物分子形成的分子间氢键,并且Phe265残基和酚类底物的芳香环形成仔-仔相互作用.量子化学计算表明,芳环上取代基的推拉电子效应显著影响协同电子转移的底物去质子化过程,其中推电子能力较强的-NH2,-OH,-OCH3和-CH CHCH3等基团能够明显增强酚羟基反应活性,而吸电子的-CONH2和-Cl则具有相反的效应.

英文摘要：

The binding affinity and reactivity between laccase and phenolic substrates were investigated with bioinformatics analysis, molecular dynamics simulation and quantum chemical calculation. Sequence and structure alignments indicate that the substrate-binding pocket of the laccases include certain conserved amino acid（AA） residues, such as Asp/Glu206, Asn/His208, Asn264, Gly392, His458（using the AA sequence number of PDB：1KYA, a laccase from Trametes versicolor）. Accordingly, the binding affinity between the laccase and the modeled 21 phenolic substrates were calculated with the MM-GBSA method. As a result of the molecular modeling, the inter-molecular hydrogen bonding between the hydroxyl group and Asp206/Asn264, and theπ-πinteraction between the phenyl group and Phe265 , are essential for binding phenolic substrates to the laccase. The quantum chemistry calculations indicate that electronic effects of the additional substituent groups on the substrates would affect reductivity significantly, in particular for the collaborative deprotonation. The electron-donating groups, such as-NH2 ,-OH,-OCH3 and-CH CHCH3 , enhance the substrate reactivity, while the electron-withdrawing groups not, e. g. C（ O） NH2 and-Cl. Our theoretical studies revealed that the binding affinity and reactivity stem from the different physiochemical nature, casting funda-mental insights to future molecular design of laccase-mediator system.