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Probe the Binding Mode of Aristololactam‐β‐D‐glucoside to Phenylalanine Transfer RNA in Silico
Author(s) -
Xiao Xingqing,
Zhao Binwu,
Yang Li,
Liang Xiaodong,
Ren Yingqian
Publication year - 2016
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201600603
Subject(s) - molecular mechanics , transfer rna , molecular dynamics , docking (animal) , in silico , chemistry , affinities , phenylalanine , binding site , molecular model , binding energy , stereochemistry , rna , computational chemistry , biochemistry , amino acid , physics , medicine , gene , nursing , nuclear physics
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‐β‐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 tRNA Phe . 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 .