CORE RESEARCH GRANT

核心研究补助金

• 批准号: 8364378
• 负责人: CHARLES L BROOKS
• 金额: $ 0.11万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8364378
• 关键词: Address; Biological; Biological Models; Biology; Biomedical Research; Charge; Chemicals; Development; Electronics; Ensure; Enzymes; Funding; Generations; Goals; Grant; High Performance Computing; Hydrogen; Investigation; Ions; Learning; Mechanics; Modeling; Molecular; National Center for Research Resources; Nucleic Acids; Performance; Principal Investigator; Proteins; Research; Research Infrastructure; Resources; Role; Source; Statistical Mechanics; System; Techniques; Testing; United States National Institutes of Health; Vacuum; base; cost; models and simulation; quantum; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The objective of this continuing Core Project is the development and testing of a new force field for interaction models of biological molecules which includes the effects of electronic charge polarization. We have explored different means for incorporating electronic polarizability into classical empirical force fields for biological molecules. We have settled on our current direction that encompasses the use of a class of polarizable models based on the quantum mechanical principal of charge equalization, and which utilizes the ideas of fluctuating charge distributions via extended systems techniques from statistical mechanics. These approaches have been fully implemented into the CHARMM1 molecular simulation and modeling package during the current grant period and will continue to be optimized for performance and functionality with other modules within CHARMM during the coming grant period. The primary task to be addressed during the pending grant period is the development of a consistent parameterization of the polarizable force field that is useful for modeling both protein and nucleic acid systems, and is compatible with the current generation CHARMM all hydrogen force fields (the version 22 and 28 force fields). To accomplish these goals, we have assembled the necessary quantum chemical tools, e.g., GAMESS/COSMO2,3 and GAMESS4, for the characterization of the "polarized" and vacuum charge distributions needed in developing polarizability parameters for protein and nucleic acid building blocks. We will use these tools to develop the needed model system parameterizations. Furthermore, we have developed a collaborative relationship with Alex MacKerell, the primary developer of the current generation CHARMM force fields, to ensure that the resulting polarizable force field will be parameterized in a manner consistent with existing force fields that do not include the effects of electronic charge polarization. Our main focus during the pending grant period will be to complete the first generation parameterization of a force field for biomolecular systems and perform testing to begin exploration of the role of electronic charge polarization in modulating interactions in proteins and nucleic acids. We are now poised to complete this parameter development, leading to the first generation of polarizable force fields for biological molecules. We note that this is not anticipated to provide force fields that are (initially) more accurate than existing mean field polarizable force fields (present generation empirical force fields). Instead, we aim to provide the basis for understanding when and where polarizable force fields are important in biology, and to learn how better to treat these situations. We are enthusiastic about the opportunities that such a class of force fields will open up to us. For example, we can anticipate that a deeper understanding of ion selectivity in enzymes and nucleic acid systems will be amenable to first principles investigation with this type of force field.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 这个持续的核心项目的目的是开发和测试 用于生物分子相互作用模型的新力场，包括 电子电荷极化的影响。 我们探索了融合电子极化性的不同方法 进入生物分子的经典经验力场。 我们有 定居在我们目前的方向上，该方向包括一系列的使用 基于量子机械主体的可极化模型 均等化，并利用电荷分配的思想 通过统计力学的扩展系统技术。 这些方法 已完全实施到CHARMM1分子模拟和建模中 在当前赠款期间的包装，并将继续优化 在Charmm中的其他模块的性能和功能 到来的赠款期。 待定赠款期间要解决的主要任务是 开发可极化力场的一致参数化 这对于对蛋白质和核酸系统进行建模非常有用，并且是 与当前一代Charmm兼容所有氢力场（ 版本22和28力场）。 为了实现这些目标，我们已经组装了 必要的量子化学工具，例如gamess/cosmo2,3和gamess4，用于 所需的“极化”和真空电荷分布的表征 在开发蛋白质和核酸构建的极化参数时 块。 我们将使用这些工具来开发所需的模型系统 参数化。 此外，我们已经建立了协作关系 与当前一代Charmm的主要开发商Alex Mackerell有关 力场，以确保所产生的极化力场将是 以与不现有的力场一致的方式进行参数 包括电子电荷极化的影响。 我们在 待定的赠款期是完成第一代 生物分子系统的力场的参数化并进行测试 开始探索电子电荷极化在 调节蛋白质和核酸的相互作用。 我们现在准备完成此参数开发，导致第一个 生物分子的可极化力场的产生。 我们注意到这一点 预计这不会（最初）提供更多的力场 比现有的平均极化力场准确（现代 经验力场）。 相反，我们旨在为 了解在生物学中何时何地，何时何地， 并了解如何更好地治疗这些情况。 我们对 这样的武力场将向我们开放的机会。 为了 例如，我们可以预期，对离子选择性有更深入的了解 酶和核酸系统将适合第一原理 使用这种类型的力场进行调查。