Laboratoire de Physico-Chimie Informatique, Unité de Chimie Physique Théorique et Structurale, University of Namur , 5000 Namur, Belgium.
Namur Medicine & Drug Innovation Center (NAMEDIC), University of Namur , 5000 Namur, Belgium.
J Chem Theory Comput. 2015 Jun 9;11(6):2813-26. doi: 10.1021/acs.jctc.5b00113. Epub 2015 May 14.
We have studied the structural, energetics, and dynamical properties of a variety of linear and circular DNA fragments using a solvent-mediated coarse-grained (CG) model of DNA with explicit ions recently developed by us [Naômé et al., J. Chem. Theory Comput., 2014, 10, 3541-3549]. We particularly examined the treatment of electrostatics and determined that a large cutoff is necessary to properly reproduce the DNA flexibility. Moreover, it is crucial to include long-ranged electrostatic interactions: a Particle Mesh Ewald scheme at low resolution is sufficient to avoid structural artifacts. We calculated the ring closure probabilities, as j-factors, for DNA fragments of different lengths from equilibrium, as well as restrained molecular dynamics (MD) simulations. The latter force integration method provided accurate results without model fitting. We generated topology and energy maps for DNA minicircles of various lengths and helical densities, at low and high ion concentrations. A general trend for structure compaction is observed, driven by an increase in writhing as the ionic concentration increases. Finally, we applied a reconstruction procedure to generate detailed molecular structures from the various superhelical conformations generated by the CG MD of the DNA minicircles. These pre-equilibrated reconstructed atomistic structures can serve as starting material for atomistic simulations.
我们使用最近由我们开发的带有显式离子的溶剂介导的粗粒 (CG) 模型 [Naômé 等人，J. Chem. Theory Comput.，2014，10，3541-3549] 研究了各种线性和圆形 DNA 片段的结构、能量和动力学特性。我们特别研究了静电处理，并确定需要大的截止值才能正确再现 DNA 的柔韧性。此外，包含长程静电相互作用至关重要：低分辨率的粒子网格 Ewald 方案足以避免结构伪影。我们从平衡状态计算了不同长度的 DNA 片段的环闭概率，即 j 因子，以及受限分子动力学 (MD) 模拟。后者的力积分方法提供了无需模型拟合的准确结果。我们在低离子和高离子浓度下生成了各种长度和螺旋密度的 DNA 小环的拓扑和能量图谱。观察到结构紧缩的一般趋势，这是由于离子浓度增加导致扭曲增加所致。最后，我们应用重建程序从 DNA 小环的 CG MD 生成的各种超螺旋构象生成详细的分子结构。这些预平衡的重建原子结构可以作为原子模拟的起始材料。
