基于分子动力学模拟研究锤头状核酶催化作用中C3和G8位点突变效应的起源
Origin of mutational effects at the C3 and G8 positions on hammerhead ribozyme catalysis from molecular dynamics simulations.
作者信息
Lee Tai-Sung, York Darrin M
机构信息
Consortium for Bioinformatics and Computational Biology, and Department of Chemistry, University of Minnesota, 207 Pleasant Street SE, Minneapolis, Minnesota 55455, USA.
出版信息
J Am Chem Soc. 2008 Jun 11;130(23):7168-9. doi: 10.1021/ja711242b. Epub 2008 May 14.
Abstract
A series of ten 60 ns molecular dynamics (MD) simulations of the native and mutated full length hammerhead ribozymes in the reactant state and in an activated precursor state (G8:2'OH deprotonated) are reported. Mutant simulations include the C3U, G8A, and G8I single mutants and a C3U/G8A double mutant that exhibits an experimental rescue effect. The results provide critical details into the origin of the observed mutation effects and support a mechanism where the 2'OH of G8 acts as a general acid catalyst that is held in position through Watson-Crick hydrogen bonding between G8 and C3.
摘要
本文报道了对处于反应物状态和活化前体状态（G8的2'-OH去质子化）的天然和突变型全长锤头状核酶进行的一系列十次60纳秒分子动力学（MD）模拟。突变模拟包括C3U、G8A和G8I单突变体以及表现出实验性拯救效应的C3U/G8A双突变体。这些结果为观察到的突变效应的起源提供了关键细节，并支持了一种机制，即G8的2'-OH作为一般酸催化剂，通过G8与C3之间的沃森-克里克氢键固定在特定位置。
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