COMPUTATIONAL STUDIES OF COMPLEX PROCESSES IN BIOLOGICAL MACROMOLECULAR SYSTEMS

生物大分子系统复杂过程的计算研究

• 批准号: 7601276
• 负责人: BENOIT ROUX
• 金额: $ 0.03万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7601276
• 关键词: Address; Algorithms; Biological; Complex; Computer Retrieval of Information on Scientific Projects Database; Development; Electrostatics; Free Energy; Funding; Glutamate Receptor; Grant; Institution; Membrane; Methods; Modeling; Motion; Phosphotransferases; Potassium Channel; Process; Range; Reaction; Research; Research Personnel; Resources; Sampling; Sampling Biases; Source; System; United States National Institutes of Health; abstracting; base; computer studies; macromolecule; molecular dynamics; parallel processing; research study; simulation; src-Family Kinases; supercomputer

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. free energy sampling simulation permeation channels kinases membranes solvation solvation Abstract: This proposal is the continuation of the projects supported by previous NRAC allocation grants. The projects exploit the advances in molecular dynamics (MD) simulations years with respect to accuracy of force fields, treatment of long-range electrostatics, efficiency of integration algorithms, parallel processing, and other technical issues. Computations based on detailed atomic models can make significant contributions to the understanding of biomolecular systems. It is, however, essential to develop special strategies to get quantitatively meaningful results that can be compared with experiments. Many questions cannot be addressed with simple ``brute force'' MD simulation methods. For example, free energy perturbation and potential of mean force (PMF) calculations with biased sampling methods along multi-dimensional reaction coordinates are an attractive method to overcome the sampling difficulties without sacrificing accuracy. The application of special strategies to large-scale motions in macromolecules remains very challenging. In the current proposal, we describe several computational projects aimed at understanding complex and diverse biological systems such as: potassium channels, tyrosine kinases of the Src family, glutamate receptor, and the development and refinement of a fully polarizable force field for biomolecular simulations using the classical Drude oscillator model. It would not be possible to make meaningful progress in these projects without access to supercomputer resources.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 自由能抽样模拟渗透通道激酶膜溶剂化摘要摘要：该建议是继续由先前NRAC分配赠款支持的项目的延续。这些项目利用了分子动力学（MD）模拟的进步，该项目在力场的准确性，远程静电治疗，整合算法的效率，并行处理和其他技术问题方面利用了。基于详细原子模型的计算可以为理解生物分子系统做出重大贡献。但是，必须制​​定特殊策略以获得定量有意义的结果，这可以与实验进行比较。许多问题无法用简单的``蛮力''MD模拟方法来解决。例如，沿多维反应坐标的自由能扰动和平均力（PMF）计算的计算是一种有吸引力的方法，可以在不牺牲准确性的情况下克服采样困难。特殊策略在大型大分子中的大规模运动中的应用仍然非常具有挑战性。在当前的提案中，我们描述了旨在了解复杂和多样化的生物系统的几个计算项目，例如：使用古典Drude振动器模型，使用古分子模拟的钾家族的钾通道，SRC家族的酪氨酸激酶，谷氨酸受体的酪氨酸激酶以及可用于生物分子模拟的完全极化力场的开发和完善。在不访问超级计算机资源的情况下，不可能在这些项目中取得有意义的进展。