高性能大规模分子动力学的前沿进展--近35年生物体系的分子动力学模拟研究回顾

Frontiers in High-Performance,Large-Scale Molecular Dynamics.35 Years of Molecular-Dynamics Simulations of Biological Systems

对近35年来数值模拟方法,特别是经典分子动力学方法和相关的优先采样技术在生物体系研究中的应用作了回顾.由于生物体系研究对象的特点是体系空间尺度大且细胞机制时间跨度长,因此所涉及的结构生物学和生物物理学方面的研究构成了分子动力学模拟的最大挑战.从生物学的角度对分子动力学的基本理论、算法发展以及在生物体系中的应用进行综述,重点阐释在生理活动相关的时间尺度上生物体系的模拟是如何逐步发展的.另一方面,回顾了生物模拟体系在空间和时间尺度上得益于计算机硬件和算法的飞速发展而急速扩张的历程.最后,基于最近生物体系分子动力学模拟领域的尖端研究成果,对该领域未来发展的趋势进行了思考和展望.

The main thrust of this contribution is to review applications of numerical simulations to biological systems over the past 35 years-specifically classical molecular-dynamics simulations and related preferential sampling approaches aimed at exploring selected degrees of freedom of the molecular assembly.Arguably enough,structural biology and biophysics represent one of the greatest challenges for molecular dynamics,owing to the size of the biological objects of interest and the time scales spanned by the molecular processes of the cell machinery in which these objects are prominent actors.The reader is assumed to be fully familiarized with the basic theoretical underpinnings of molecular-dynamics simulations,which will be discussed here from a biological standpoint,emphasizing how the enterprise of modeling increasingly larger molecular assemblies over physiologically relevant times has shaped the field.This review article will further show how the unbridled race to dilate both the spatial and the temporal scales,in an effort to bridge the gap between the latter,has greatly benefitted from groundbreaking advances on the hardware,computational front-notably through the development of massively parallel and dedicated architectures,as well as on the methodological,algorithmic front.The current trends in this research field,boosted by recent,cutting-edge achievements,wherein molecular dynamics has reached new frontiers,provide the basis for an introspective reflection and a prospective outlook into the future of biologically-oriented,high-performance numerical simulations.Furthermore,alternatives to brute-force molecular dynamics towards connecting time and size scales will be discussed,in particular a class of approaches relying upon the preferential sampling of judiciously chosen,important degrees of freedom of the biological object at hand.These methods,targeted primarily at providing a detailed thermodynamic picture of the molecular process at hand,can be viewed as computational tweezers designed to dissect the latter by means of a reduced set of collective variables.