High-level QM/MM free energy calculations and reaction path studies at affordable computational cost

以可承受的计算成本进行高级 QM/MM 自由能计算和反应路径研究

• 批准号: 1464946
• 负责人: Henry Woodcock
• 金额: $ 41.1万
• 依托单位: University of South Florida
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-15 至 2020-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1464946&HistoricalAwards=false
• 关键词: level; QM; MM; free; energy

Henry Lee Woodcock of the University of South Florida is supported by an award from the Chemical Theory, Models and Computational Methods program in the Chemistry Division to develop the next generation of accurate and efficient methodology to simulate reactive chemical systems in solution. Solvent plays a major role in governing chemical processes and must be taken into account to construct accurate models. It is much more difficult to study chemical reactions in solution than to study reactions of isolated or gas phase molecules. Woodcock and his coworkers focus on the development of open-sourced Web-based software (www.charmming.org) to facilitate molecular simulation. The software development efforts are tightly coupled to education and outreach activities aimed at making advanced molecular simulation techniques more accessible to modeling newcomers and the non-technical expert. Education and outreach related developments are incorporated into the physical chemistry curriculum at several universities. Woodcock and his research group collaborate extensively with a leading expert in the field, Professor Stefan Boresch at the University of Vienna in Austria. This research is cofunded by the Office of International Science and Engineering and the Computational Science and Engineering (CDS&E) program in the Division of Advanced Cyberinfrastructure.Accurately computing free energies is one of the most challenging problems facing chemists. It is well known that solvent plays a major role in governing chemical processes and must be takeninto account to construct accurate models. The hybrid quantum mechanical / molecular mechanical (QM/MM) framework is the current tool of choice when accurate computations of macromolecular systems are essential. However, robust and efficient approaches that employ the high levels of computational theory needed to accurately describe many reactive processes while also including explicit solvation effects and accounting for extensive conformational sampling are essentially non-existent. The main goal this project is the development of techniques that mitigate current computational limitations related to accuracy, efficiency, and adequate sampling in such calculations. These methods are applied to study two key processes that are fundamental to understanding structure and stability across a range of solvated bio-organic compounds.

南佛罗里达大学的Henry Lee Woodcock获得了化学部化学理论、模型和计算方法项目的支持，以开发准确和高效的下一代方法来模拟溶液中的活性化学体系。溶剂在控制化学过程中起着主要作用，必须考虑到这一点才能建立准确的模型。研究溶液中的化学反应比研究孤立分子或气相分子的反应困难得多。Woodcock和他的同事们专注于基于Web的开源软件(www.charmming.org)的开发，以促进分子模拟。软件开发工作与教育和推广活动紧密相连，旨在使先进的分子模拟技术更容易为建模新手和非技术专家所用。在几所大学，与教育和推广相关的发展被纳入物理化学课程。Woodcock和他的研究小组与该领域的领先专家、奥地利维也纳大学的Stefan Boresch教授进行了广泛的合作。这项研究是由国际科学与工程办公室和高级网络基础设施部门的计算科学与工程(CDS&Amp；E)计划共同资助的。准确地计算自由能是化学家面临的最具挑战性的问题之一。众所周知，溶剂在控制化学过程中起着重要作用，必须考虑溶剂才能建立准确的模型。当对大分子体系进行精确计算时，混合量子力学/分子力学(QM/MM)框架是当前选择的工具。然而，使用高水平的计算理论来准确描述许多反应过程，同时还包括显式溶剂化效应和考虑广泛的构象采样的稳健和高效的方法基本上是不存在的。这个项目的主要目标是开发技术，以缓解目前与此类计算中的准确性、效率和足够采样有关的计算限制。这些方法被应用于研究两个关键过程，这两个过程是了解一系列溶剂化生物有机化合物的结构和稳定性的基础。