论文标题

分子动力学中的刚性碱基偏置可以增强DNA构象的采样

Rigid Base Biasing in Molecular Dynamics enables enhanced sampling of DNA conformations

论文作者

Voorspoels, Aderik, Vreede, Jocelyne, Carlon, Enrico

论文摘要

全原子模拟在研究核酸准确并提供高空间和时间分辨率的核酸的构象和动力学特性变得越来越流行。然而,这种高分辨率的计算成本很高,在模拟的时间尺度内,核酸的时间尺度在其理想结构周围较弱波动,探索了有限的构象。我们引入了RBB-NA算法,该算法能够控制核酸的全原子模拟中的刚性碱基参数。有了合适的偏见势,该算法可以“强制” DNA或RNA分子假设六个旋转的特定值(倾斜,滚动,扭曲,扣子,扣子,螺旋桨,开口)和/或六个转换参数(移位,幻灯片,上升,上升,上升,剪切,剪切,剪切,拉伸,stagger,stagger,Stagger)。该算法能够使用高级抽样技术探测局部强烈变形的核酸的结构和动力学。我们说明了它的性能,显示了一些示例,其中DNA强烈扭曲,弯曲或局部弯曲。在这些示例中,RBB-NA很好地再现了无约束的模拟数据和DNA力学的其他已知特征,但它也允许人们探索表征高变形状态下核酸力学的非谐波行为。

All-atom simulations have become increasingly popular to study conformational and dynamical properties of nucleic acids as they are accurate and provide high spatial and time resolutions. This high resolution however comes at a heavy computational cost and within the time scales of simulations nucleic acids weakly fluctuate around their ideal structure exploring a limited set of conformations. We introduce the RBB-NA algorithm which is capable of controlling rigid base parameters in all-atom simulations of Nucleic Acids. With suitable biasing potentials this algorithm can "force" a DNA or RNA molecule to assume specific values of the six rotational (tilt, roll, twist, buckle, propeller, opening) and/or the six translational parameters (shift, slide, rise, shear, stretch, stagger). The algorithm enables the use of advanced sampling techniques to probe the structure and dynamics of locally strongly deformed Nucleic Acids. We illustrate its performance showing some examples in which DNA is strongly twisted, bent or locally buckled. In these examples RBB-NA reproduces well the unconstrained simulations data and other known features of DNA mechanics, but it also allows one to explore the anharmonic behavior characterizing the mechanics of nucleic acids in the high deformation regime.

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