Enabling long timestep molecular dynamics on parallel CPU and GPU environments

描述（由申请人提供）：要求支持开发和实施用于模拟蛋白质长时间步动力学的新型计算方法，并将这些方法应用于研究柔性蛋白质中运动和生物功能之间的关系。这将满足对高保真方法的迫切需求，这种方法可以达到微秒到毫秒的生物学相关时间尺度的模拟，而不是通常可用的纳秒到微秒的模拟。虽然构象变化本身已经进行了多年的计算研究，但我们提出的工作与其他方法的不同之处在于：(1)长时间步长的新方法的高性能实现和全原子分辨率的增强采样；(2)这些详细方法的应用，以解决与生物医学相关的生物分子的灵活性和功能问题。由于与实验的定量比较对于我们的计算方法的测试和更大的影响都是至关重要的，因此提出了实验合作。这些都是由支持信记录的。该项目将对nih资助的研究人员产生广泛的影响，因为目标并行软件包已经拥有大量的用户基础，并且具有开放的源代码。更长的MD模拟将允许在蛋白质折叠、蛋白质工程、酶设计、针对灵活靶点的药物设计以及蛋白质和核酸复合物之间的相互作用等领域进行以前不可能进行的研究。

DESCRIPTION (provided by applicant): Support is requested for the development and implementation of novel computational methods for simulating the long timestep dynamics of proteins and the application of these methods to study the relation between motions and biological functions in flexible proteins. This will satisfy an urgent need for high-fidelity methos that reach biologically relevant timescales of microseconds to milliseconds of simulation, rather than the nanoseconds to microseconds simulations that are commonly available. While conformational change has itself been studied computationally for many years, our proposed work differs from other approaches in (1) the high-performance implementation of novel methods for long timestep dynamics and enhanced sampling at all-atom resolution and (2) the application of these detailed methods to address questions of flexibility and function in biomolecules of biomedical relevance. Since a quantitative comparison to experiment is critical for both the testing and greater impact of our computational methods, experimental collaborations are proposed. These are documented by letters of support. This project will have a widespread impact on NIH-funded researchers because the target parallel software packages already have a large user base and have an open code source. Longer MD simulations will allow previously impossible studies to be carried out in the fields of protein folding, protein engineering, enzyme design, drug design to flexible targets, and interactions among protein and nucleic acid complexes.