标题：QM/MM Study on the Reaction Mechanism of O~6-AlkyIguanine-DNA Alkyltransferase
作者：Qianqian Hou;Likai Du;Jun Gao
作者机构：[Hou, Q] Key Lab of Colloid and Interface Chemistry, Shandong University, Ministry of Education, Jinan, Shandong 250100, China;[ Du, L] Key Lab of Col 更多
通讯作者地址：[Liu, YJ]Shandong Univ, Key Lab Colloid & Interface Chem, Minist Educ, Sch Chem & Chem Engn, Jinan 250100, Shandong, Peoples R China.
来源：The journal of physical chemistry, B. Condensed matter, materials, surfaces, interfaces & biophysical
摘要：Combined quantum-mechanical/molecular-mechanical (QM/MM) approaches have been applied to investigate the detailed reaction mechanism of human O~6-alkylguanine-DNA alkyltransferase (AGT). AGT is a direct DNA repair protein that is capable of repairing alkylated DNA by transferring the methyl group to the thiol group of a cysteine residue (Cys145) in the active site in an irreversible and stoichiometric reaction. Our QM/MM calculations reveal that the methyl group transferring step is expected to occur through two steps, in which the methyl carbocation generating step is the rate-determining step with an energy barrier of 14.4 kcal/mol at the QM/MM B3LYP/6-31G(d,p)//CHARMM22 level of theory. It is different from the previous theoretical studies based on QM calculations by using a cluster model in which the methyl group transferring step is a one-step process with a higher energy barrier.