Base pair opening within B-DNA:: free energy pathways for GC and AT pairs from umbrella sampling simulations
Base pair opening within B-DNA:: free energy pathways for GC and AT pairs from umbrella sampling simulations
复制标题
DOI：
10.1093/nar/gkg239
复制
发表时间：
2003-03-01
影响因子：
14.9
通讯作者：
Lavery, R
中科院分区：
文献类型：
--
作者：
Giudice, E;Várnai, P;Lavery, R
利用伞形采样分子动力学模拟方法研究了B-DNA双链体碱基在大、小沟中的构象路径和自由能变化。我们比较GC和AT碱基对开放的双链D（GAGAGAGAGAGAG）。d（CTCTCTCTCTCTCTC）寡聚体，我们也能够研究开放的构象和动态性质的DNA和周围的溶剂的影响。结果表明，一个两阶段的开放过程与初始耦合的运动的基地内的扰动碱基对。在嘧啶碱基的情况下，大沟和小沟途径在能量上是相当的，但是大沟途径有利于较大的嘌呤碱基。碱基开放与特定骨架二面角的变化和某些螺旋扭曲（包括解旋和弯曲）有关，尽管所有这些效应都取决于所涉及的特定碱基。部分开放也导致定义明确的水桥位点，这可能在稳定扰动碱基对中发挥作用。
The conformational pathways and the free energy variations for base opening into the major and minor grooves of a B-DNA duplex are studied using umbrella sampling molecular dynamics simulations. We compare both GC and AT base pair opening within a double-stranded d(GAGAGAGAGAGAG). d(CTCTCTCTCTCTC) oligomer, and we are also able to study the impact of opening on the conformational and dynamic properties of DNA and on the surrounding solvent. The results indicate a two-stage opening process with an initial coupling of the movements of the bases within the perturbed base pair. Major and minor groove pathways are energetically comparable in the case of the pyrimidine bases, but the major groove pathway is favored for the larger purine bases. Base opening is coupled to changes in specific backbone dihedrals and certain helical distortions, including untwisting and bending, although all these effects are dependent on the particular base involved. Partial opening also leads to well defined water bridging sites, which may play a role in stabilizing the perturbed base pairs.