Chen Y Z, Mohan V, Griffey R H
ISIS Pharmaceuticals, Carlsbad, CA 92008, USA.
J Biomol Struct Dyn. 1998 Feb;15(4):765-77. doi: 10.1080/07391102.1998.10508991.
In this work we explore the possibility of the opening of a single base without perturbation of its neighboring nucleotides. Low energy base opening into the grooves can be accomplished by rotation of the relevant backbone and glycosidic bond torsion angles. The pathway has been determined by identifying zeta torsion angle as the reaction coordinate together with the accompanying geometric requirement that guides the displacement of other torsion angles. Our study on Dickerson dodecamer duplex d(CGCGAATTCGCG)2 showed that all bases with normal equilibrium zeta can be rotated by approximately 30 degrees, corresponding to approximately 3.5A base displacement, towards the major groove. Such an opening extent is comparable with estimated amplitudes of local angular motions in DNA bases from NMR experiments, which might facilitate proton exchange. The computed base opening energy barrier is also comparable with measured base pair opening enthalpy. These results indicate possible relevance of the pathway studied in this work with experimentally observed base pair opening process. Our analysis also showed a preference for base opening along the major groove and an abnormal opening behavior for bases with unusual equilibrium zeta torsion angle.
在这项工作中，我们探索了在不干扰相邻核苷酸的情况下打开单个碱基的可能性。通过相关主链和糖苷键扭转角的旋转，可以实现低能量碱基向沟槽的打开。通过将ζ扭转角确定为反应坐标以及伴随的指导其他扭转角位移的几何要求，确定了该途径。我们对Dickerson十二聚体双链体d(CGCGAATTCGCG)₂的研究表明，所有具有正常平衡ζ的碱基都可以朝着大沟旋转约30度，对应于约3.5埃的碱基位移。这样的打开程度与核磁共振实验中DNA碱基局部角运动的估计幅度相当，这可能有助于质子交换。计算得到的碱基打开能垒也与测量得到的碱基对打开焓相当。这些结果表明，这项工作中研究的途径可能与实验观察到的碱基对打开过程相关。我们的分析还表明，碱基倾向于沿着大沟打开，并且具有异常平衡ζ扭转角的碱基具有异常的打开行为。
