SI2-SSE: Enabling Chemical Accuracy in Computer Simulations: An Integrated Software Platform for Many-Body Molecular Dynamics

该项目由高级数字基础设施办公室和数学和物理科学局内的化学司共同资助。正如2013年诺贝尔化学奖授予Martin Karplus、Michael Levitt和Arieh Warshel所证明的那样，分子水平的计算机模拟在许多研究领域中已经变得不可或缺，包括化学、物理、材料科学和生物化学，并且经常提供本来很难获得的基本见解。如今，计算机模拟被用来补充、指导，有时甚至取代实验测量，减少了将实验室想法转化为实际应用的研究所花费的时间和金钱。在制药工业中，计算机模拟在基于结构的药物设计中发挥着关键作用，HIV蛋白酶抑制剂的开发证明了这一点。在化学工业中，计算机建模指导设计新的催化剂以及应用于更高效的电池、燃料和太阳能电池的新材料。最近，在利用计算机模拟设计更有效的化学过程以及提供关于安全问题的信息方面取得了重大成功。然而，分子水平的计算机模拟的真实性和预测能力直接取决于描述分子之间相互作用的准确性。为了解决现有模拟方法的局限性，项目组最近开发了一种新的理论/计算方法，该方法已被证明在应用于各种分子系统时表现出前所未有的准确性。拟议研究的首要目标是将这一新方法落实到一个综合的公开可用的软件平台中，使科学界能够通过计算机模拟解决广泛的问题。潜在的应用包括，但不限于，新药物和新材料的合理设计，用于水净化和有毒化合物和爆炸物的检测，更有效的化学过程的催化剂的虚拟筛选，新电池、太阳能和燃料电池的开发，以及生物分子结构预测。一群不同的高中生、本科生和研究生将直接参与拟议研究的不同方面。因此，学生将获得计算机模拟和编程的关键知识，这将大大增强他们在当今计算机驱动的就业市场上的竞争力。鉴于其多学科和多方面的性质，拟议的研究将促进不同层面的科学进步，并有助于新技术的发展，以促进国家健康、繁荣和福利，并确保国防安全。拟议的研究重点是开发和实施独特的软件元素，这些软件元素将使用Pesani小组开发的所谓多体分子动力学(MB-MD)方法在CPU和GPU架构上进行计算机模拟。这些软件要素将通过一个综合平台向科学界公开提供。MB-MD是一种新的模拟方法，已被证明在从气体到凝聚相的各种分子体系的分子模拟中提供了前所未有的准确性。新的软件元素包括集成在一个独特的软件平台中的三个组件：一套公开可用的计算工具，用于根据电子结构数据自动生成多体势能函数；一个客户端-服务器架构，用于通过志愿者计算计算所需的电子结构数据；用于OpenMM工具包的独立CPU和GPU插件，将使MB-MD能够跨不同阶段模拟通用分子体系。在开展拟议的研究和软件工程项目的同时，还开展了外联和辅导活动，通过国际和平协会和共同国际联合会直接参与加州大学圣地亚哥分校和圣地亚哥超级计算机中心的几个外联项目，在贫困和代表性不足的少数族裔学生中推广STEM学科。这些活动是专门为提高妇女、少数群体和经济弱势群体从高中到本科生和研究生的不同教育水平的参与度和地位而设计的。

This project is jointly funded by the Office of Advanced Cyberinfrastructure and and the Division of Chemistry within the Directorate of Mathematical and Physical Sciences. As attested by the 2013 Nobel Prize in Chemistry awarded to Martin Karplus, Michael Levitt, and Arieh Warshel, molecular-level computer simulations have become indispensable in many research areas, including chemistry, physics, materials science, and biochemistry, and often provide fundamental insights that are otherwise difficult to obtain. Nowadays, computer simulations are used to complement, guide, and sometimes replace experimental measurements, reducing the amount of time and money spent on research to bring ideas from the lab to practical applications. In the pharmaceutical industry computer simulations play a key role in structure-based drug design as demonstrated by the development of HIV protease inhibitors. In the chemical industry, computer modeling guides the design of new catalysts as well as novel materials for applications in more efficient batteries, and fuel and solar cells. More recently, there has been significant success in using of computer simulations to design more effective chemical processes as well as to provide information on safety issues. However, both the realism and the predictive power of a molecular-level computer simulation directly depend on the accuracy with which the interactions between molecules are described. To address the limitations of existing simulation approaches, the project group has recently developed a new theoretical/computational methodology that has been shown to display unprecedented accuracy when applied to a variety of molecular systems. The overarching goal of the proposed research is the implementation of this new methodology into an integrated and publicly available software platform that will allow the scientific community to address a broad range of problems through computer simulations. Potential applications include, but are not limited to, the rational design of new drugs as well as novel materials for water purification and the detection of toxic compounds and explosives, the virtual screening of catalysts for more efficient chemical processes, the development of new batteries, solar and fuel cells, and biomolecular structure prediction. A diverse group of high school, undergraduate, and graduate students will be directly involved in different aspects of the proposed research. The students will thus acquire critical knowledge about computer simulations and programming, which will significantly enhance their competitiveness in today's computer-driven job market. Given its multidisciplinary and multifaceted nature, the proposed research will promote scientific progress at different levels and contribute to the development of new technologies that will advance the national health, prosperity and welfare, as well as secure the national defense.The proposed research focuses on the development and implementation of unique software elements that will enable computer simulations on both CPU and GPU architectures using the so-called many-body molecular dynamics (MB-MD) methodology developed by the Paesani group. These software elements will be made publicly available to the scientific community through an integrated platform. MB-MD is a new simulation methodology that has already been shown to provide unprecedented accuracy in molecular simulations of a variety of molecular systems from the gas to the condensed phase. The new software elements comprise three components integrated in a unique software platform: a suite of publicly available computational tools for the automated generation of many-body potential energy functions from electronic structure data; a client-server architecture for the calculation of the required electronic structure data through volunteer computing; independent CPU and GPU plugins for the OpenMM toolkit which will enable MB-MD simulations of generic molecular systems across different phases. In parallel with the proposed research and software engineering projects, outreach and mentoring activities to promote STEM disciplines among students from underprivileged and underrepresented minorities through the PI and Co-PI direct involvement in several outreach programs at UC San Diego and the San Diego Supercomputer Center. These activities are specifically designed to increase the involvement and advancement of women, minorities, and economically disadvantaged groups across different education levels, from high school to undergraduate and graduate students.