SI2-SSE: Software Tools for Biomolecular Free Energy Calculations

技术总结网络基础设施办公室、材料研究司、化学司以及土木工程、机械和制造创新司为该奖项提供资金，该奖项是根据向软件基础设施持续创新征集提出的建议而设立的。该奖项支持开发一套新的软件工具，用于计算生物分子自由能、跃迁路径和反应速率，这些工具将基于并将增强PI的aBMD/REMD/SMD代码套件。新的功能将被添加到现有的代码中，这应该会极大地增强软件对挑战生物分子问题的适用性。具体而言，PIS旨在实施和发展：(I)处理动态耦合的多个步行器或复制品以进行强化采样的能力；(Ii)引入用于计算反应速率和相关物理量的过渡路径理论和采样方法；以及(Iii)引入用于多维自由能计算和重要的最小自由能路径计算的“弦方法”。这些软件工具将在开源GPL下发布，并作为Amber软件包的一部分发布。这些代码还将作为独立的模块通过网络发布，供其他用户集成到他们自己的程序中。为了测试和展示软件包的工作原理，PI将这些方法应用于手性变化起重要作用的生物分子系统，包括：富含脯氨酸的系统，主要是胶原和一种新的细胞穿透肽，以及B和Z双螺旋中的DNA和RNA。该奖项还将通过以下方式加强教育：指导和招收少数族裔学生，开发生物物理学选项，将研究主题整合到当前的教育论坛中，与当地学校合作，并开发一个新的计算科学和工程研究所。非技术总结网络基础设施办公室，材料研究司，化学司，以及土木、机械和制造创新司为该奖项提供资金，该奖项是根据向软件基础设施持续创新征集提出的提案而设立的。该奖项支持开发一套新的软件工具，使计算涉及生物分子的化学反应速率成为可能。这些代码还将能够计算在生化系统中可以转化为有用功的能量。这些代码将通过一个被广泛使用的名为Amber的软件包分发，该软件包为计算化学、生物化学、化学工程、材料和生物物理学社区的软件网络基础设施做出贡献。它将使涉及生物分子的广泛计算研究成为可能。其中可能的应用包括研究生物分子的结构和转化，提供有关其可能功能的信息，模拟抗生素，以及模拟纳米技术的应用。该奖项还将通过以下方式加强教育：指导和招收少数族裔学生，开发生物物理学选项，将研究课题纳入当前的教育论坛，与当地学校合作，以及建立一个新的计算科学和工程研究所。

TECHNICAL SUMMARYThe Office of Cyberinfrastructure, Division of Materials Research, Chemistry Division, and Division of Civil, Mechanical, and Manufacturing Innovation contribute funds to this award made on a proposal to the Software Infrastructure for Sustained Innovation solicitation. This award supports the development of a new set of software tools for calculating biomolecular free energies, transition paths, and reaction rates that will be based on and will augment the PIs' ABMD/REMD/SMD suite of codes. New capabilities are to be added to the existing codes, which should greatly enhance the applicability of the software to challenging biomolecular problems. In particular, the PIs aim to implement and develop: (i) the capability for dealing with dynamically coupled multiple walkers or replicas for enhanced sampling; (ii) the introduction of Transition Path Theory and Sampling methodology for calculating reaction rates and related physical quantities; and (iii) the introduction of the "string method" for multi-dimensional free energy calculations and the calculation of the important minimum free energy path. These software tools will be released under the open source GPL, and released as part of the AMBER software package. The codes will also be released as stand-alone modules via the web for other users to integrate into their own programs.To test and showcase the workings of the software package, the PIs will apply these methods to biomolecular systems where changes in handedness play an important role, including: proline-rich systems, mainly collagen and a new class of cell-penetrating peptides, and DNA and RNA in B and Z double helices. This award will also enhance education through: the mentoring and recruitment of minority students, the development of a Biophysics option, the integration of research topics into current educational forums, working with local schools, and the development of a new Institute for Computational Science and Engineering.NON-TECHNICAL SUMMARYThe Office of Cyberinfrastructure, Division of Materials Research, Chemistry Division, and Division of Civil, Mechanical, and Manufacturing Innovation contribute funds to this award made on a proposal to the Software Infrastructure for Sustained Innovation solicitation. This award supports the development of a new set of software tools that will enable the calculation of rates of chemical reactions involving biomolecules. The codes will also be able to calculate the energy that can be converted into useful work in a biochemical system. The codes will be distributed through a widely used software package called AMBER which contributes to the software cyberinfrastructure of computational chemistry, biochemistry, chemical engineering, materials, and biological physics communities. It will enable a wide range of computational research involving biological molecules. Among the possible applications are the study of the structure and transformations of biomolecules which provides information on their possible functions, the simulation of antibiotics, and simulating nanoscale technology applications. This award will also enhance education through: the mentoring and recruitment of minority students, the development of a Biophysics option, the integration of research topics into current educational forums, working with local schools, and the development of a new Institute for Computational Science and Engineering.