文献类型：期刊文献

英文题名：Probe the Binding Mode of Aristololactam-β-D-glucoside to Phenylalanine Transfer RNA in Silico

作者：Xiao, Xingqing[1,4,5];Zhao, Binwu[1];Yang, Li[2,4,5];Liang, Xiaodong[3];Ren, Yingqian[4,5]

机构：[1]North Carolina State Univ, Dept Chem & Biomol Engn, Raleigh, NC 27695 USA;[2]Wuhan Inst Technol, Minist Educ, Key Lab Green Chem Proc, Sch Chem Engn & Pharm,Key Lab Novel Reactor & Gre, Wuhan 430073, Hubei, Peoples R China;[3]Tech Univ Denmark, Ctr Energy Resources Engn, Dept Chem & Biochem Engn, DK-2800 Lyngby, Denmark;[4]East China Univ Sci & Technol, State Key Lab Chem Engn, Shanghai 200237, Peoples R China;[5]East China Univ Sci & Technol, Dept Chem, Shanghai 200237, Peoples R China

年份：2016

卷号：1

期号：17

起止页码：5430

外文期刊名：CHEMISTRYSELECT

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000395425400007)】；

基金：Financial support for this work was provided by the National Natural Science Foundation of China (No. 21406172) and the China Scholarship council. We would like to thank NC State University High Performance Computing Center for providing us computing software and time.

语种：英文

外文关键词：Aristololactam-beta-D-glucoside; Binding of drug molecule and RNA; Molecular docking and simulations; Molecular recognition mechanism; Phenylalanine transfer RNA

摘要：Understanding the interactions of drug molecules with biomacromolecules at a micro-scale level is essential to design potent drugs for the treatments of human genome diseases. To unravel the mechanism of binding of aristololactam-beta-D-glucoside (ADG) and phenylalanine transfer RNA (tRNA(Phe)), an integrated computational strategy combining quantum mechanics (QM) calculation, molecular docking and atomistic molecular dynamics (MD) simulation was present in this work. QM calculations were performed to derive the partial charges of ADG, molecular docking was used to determine the binding poses of ADG on the tRNA(Phe), and atomistic MD simulations were conducted to examine the thermal stability of five predicted binding poses for the complex of ADG and the tRNAPhe. The binding free energies of the five complexes were then calculated using the molecular mechanics/generalized born surface area approach with the variable internal dielectric constant model. By comparing computed affinities and experimentally- measured values in the binding free energy, we identified a most likely binding structure of ADG and the tRNA(Phe). Further analysis of energy of the ADG-tRNA complex revealed that the aristololactam of ADG provides binding specificity to the tRNA(Phe), and the D-glucoce contributes to the affinity for binding with the tRNA(Phe).