中文摘要：

采用QM（PM3）/MM分子动力学（MD）方法模拟了烟酰胺酶催化烟酰胺水解脱氨形成烟碱酸的反应过程.计算结果表明,硫的亲核进攻是整个反应的速率控制步骤.当改变Ala155所在Loop区的位置,在亲核进攻时,底物能够自由旋转,可以加速亲核进攻过程并降低整个催化反应的能垒.讨论了氨分子的离去过程和质子传递过程的相关细节.为烟酰胺酶的定点突变以及脱氨酶的设计提供了有益的参考.

英文摘要：

The deamination process of nicotinamide to nicotinic acid by nicotinamidase simulated with combined QM（ PM3 ）/MM molecular dynamics （MD） method. Our calculated results show that the whole mechanism includes four steps, transition of Hs, nucleophilic attack by sulfur group, nucleophilic attack by hydroxyl group and proton transfer from Aspl6 to Cys159. The rate-determined step is the nucleophilic attack by sulfur group. Through conformational analyses, we are able to indicate that high energy consumption mainly because the nucleophilic attack needs to break the hydrogen bond between substrate and Ala155. We suggest that mutation of the loop, which make Ala155 far from nicotinamide, could weaken the hydrogen bond and in- crease the reactivity of nicotinamidase. Based on this ground, release of ammonia and proton transfer processes are discussed in details. The results could give some useful suggestions to enzyme design and site-directed mutagenesis studies.