GromEx: Highly Scalable Unified Long-Range Electrostatics and Flexible Ionization for Realistic Biomolecular Simulations on the Exascale

以理论物理和化学为基础的计算机模拟已经发展成为研究分子功能和结构的宝贵工具。这种模拟与其他强相互作用系统（如天体物理学）的模拟有共同的挑战。因此，将分子模拟领域推进到百亿亿次计算对科学和公众都是非常有益的。分子模拟中最昂贵的部分是静电远程相互作用的计算。因此，计算这些相互作用的效率对整个模拟是决定性的。分子静电学是复杂的，因为分子可以包含电荷分布随时间变化的可滴定位点。这种可变性源于质子化或氧化还原反应，或不同药物分子的结合。这些反应错综复杂地与静电耦合，对许多（生物）分子的功能和相互作用特性至关重要。因此，在生物分子模拟中对静电的现实处理必须考虑到不同形式的可滴定位点。粒子网格Ewald方法（PME，目前分子模拟的最新技术）由于存在通信瓶颈，并且不能有效地处理可滴定的位点，因此不能扩展到大的核心计数。在这个项目中，我们将快速多极方法（FMM）与lambda动力学方法结合起来，既缓解了PME瓶颈，又首次在分子模拟中实现了可滴定位点的真实化学变异性。FMM将能够在大规模并行百亿亿次计算机上有效地计算远程相互作用，包括代表各种可滴定点形式的替代电荷分布。lambda动力学允许在模拟过程中在位点形式之间进行平滑的相互转换，这对于高效、完全原子化的分子模拟是必不可少的。在第二个资助期，我们的目标是为分子模拟开辟一个全新的应用范围，无论是在可以以最佳性能利用的硬件方面，还是在可以解决的科学问题类型方面。具体我们将：1。扩展当前代码以允许每个站点的多个本地拓扑。这将使模拟能够解释可滴定位点的整个变异性范围，而不仅仅是质子化2。使我们的求解器能够充分利用未来的百亿亿级硬件，包括多核cpu和加速器，如gpu或Xeon Phi协处理器3。为了在这种异构硬件上实现最佳扩展，我们将设计和实现一个基于图的分区方案，根据可用硬件设备的延迟和吞吐量从算法替代方案中进行选择。示例应用包括计算药物设计和纳米机器功能模拟。

Computer simulations on the basis of theoretical physics and chemistry have grown to be invaluable tools of scientific research on molecular function and structure. Such simulations share common challenges with simulations on other strongly interacting systems, e.g. in astrophysics. Advancing the field of molecular simulation to exascale computing is thus highly beneficial to science and the public. The most costly part of molecular simulations is the computation of electrostatic long-range interactions. Thus, the efficiency of calculating these interactions is decisive for the whole simulation. Molecular electrostatics is complicated by the fact that molecules can contain titratable sites whose charge distribution varies over time. This variability originates, e.g., from protonation or redox reactions, or binding of different drug molecules. These reactions are intricately coupled to electrostatics as well as crucial for the function and interaction properties of many (bio)molecules. Thus, a realistic treatment of electrostatics in biomolecular simulation has to account for the different forms of titratable sites. The particle mesh Ewald method (PME, currently state of the art in molecular simulation) does not scale to large core counts as it suffers from a communication bottleneck, and does not treat titratable sites efficiently. In this project, we combine a fast multipole method (FMM) with a lambda-dynamics method to both alleviate the PME bottleneck and, for the first time, enable realistic chemical variability of titratable sites in molecular simulations. The FMM will enable an efficient calculation of long-range interactions on massively parallel exascale computers, including alternative charge distributions representing various forms of titratable sites. lambda-dynamics allows for a smooth interconversion between site forms during the simulation which is indispensable for efficient, fully atomistic molecular simulations. In the second funding period, we aim to open up a whole new application range for molecular simulation, both in terms of the hardware that can be utilized at optimum performance and in terms of the type of scientific problems that can be addressed. In detail we will: 1. Extend the current code to allow for multiple local topologies of each site. This will let simulations account for the whole range of variability of titratable sites instead of just protonation 2. Enable our solver to take full advantage of future exascale hardware including many-core CPUs and accelerators like GPUs or Xeon Phi coprocessors 3. For optimum scaling on this heterogeneous hardware, we will design and implement a graph- based partitioning scheme to choose from algorithmic alternatives according to latency and throughput of the available hardware devices Example applications include computational drug design and simulations on the function of nanomachines.