Giudice Emmanuel, Várnai Péter, Lavery Richard
Laboratoire de Biochimie Théorique, CNRS UPR 9080, Institut de Biologie Physico-Chimique, 13 rue Pierre et Marie Curie, Paris 75005, France.
Nucleic Acids Res. 2003 Mar 1;31(5):1434-43. doi: 10.1093/nar/gkg239.
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.
使用伞形采样分子动力学模拟研究了B-DNA双链体中碱基向大沟和小沟开放的构象途径和自由能变化。我们比较了双链d(GAGAGAGAGAGAG)*d(CTCTCTCTCTCTC)寡聚物中GC和AT碱基对的开放情况,并且还能够研究开放对DNA的构象和动力学性质以及周围溶剂的影响。结果表明存在一个两阶段的开放过程,在受扰动的碱基对内碱基运动存在初始耦合。对于嘧啶碱基,大沟和小沟途径在能量上相当,但对于较大的嘌呤碱基,大沟途径更受青睐。碱基开放与特定主链二面角的变化以及某些螺旋畸变(包括解旋和弯曲)相关联,尽管所有这些效应都取决于所涉及的特定碱基。部分开放还会导致明确的水桥连位点,这可能在稳定受扰动的碱基对中发挥作用。