GNEIMO: Generalized Internal Coordinate Molecular Dynamics Methods

GNEIMO：广义内坐标分子动力学方法

• 批准号: 7389080
• 负责人: Nagarajan Vaidehi
• 金额: $ 31.79万
• 依托单位: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7389080
• 关键词: Address; Algorithms; Biological Process; California; Communities; Computer software; Development; Drug Formulations; Equation; Foundations; Freedom; Freezing; Frequencies; Future; Generations; Graph; Hand; Homology Modeling; Illinois; Length; Letters; Methods; Modeling; Molecular Conformation; Motion; Muscle Rigidity; Neurotoxins; Numbers; Object Attachment; Peptides; Performance; Plague; Principal Investigator; Process; Protein Structure Initiative; Proteins; Publishing; Qualifying; Range; Rate; Research; Robotics; Sampling; Spacecraft; Structural Models; System; Systematic Bias; Techniques; Testing; Time; Universities; Validation; Work; base; computer framework; computerized tools; experience; fasciculin 2; improved; mathematical algorithm; molecular dynamics; nanosecond; protein folding; protein structure; simulation; stem; structural biology; tool

DESCRIPTION (provided by applicant): Molecular dynamics (MD) simulations is a powerful computational tool in structural biology, widely used for understanding conformational changes in proteins, and folding of peptides. However MD simulations using Cartesian dynamics model is limited by the total simulation time scale being in tens of nanoseconds for large proteins. Biological processes on the other hand need microseconds of simulation time. Internal Coordinate Molecular Dynamics (ICMD) algorithms have been developed to enable larger simulation time-steps and they show great promise in long time scale simulations. Despite their promise, ICMD techniques have made little progress due in large part to the additional mathematical complexity of internal coordinate models. We propose to address and solve the key bottleneck problems with ICMD algorithms. We propose to develop, validate Generalized NEIMO (GNEIMO) ICMD methods that allow freezing of only bond lengths, bond angle and bond lengths and use of ICMD methods for wider conformational search using model coarsening strategies. We also propose to characterize the performance of ICMD algorithms for the applications such as 1) maintaining the native protein structure, 2) refinement of a near native homology structural models, 3) folding of alpha helical and beta hairpin peptides and 4) conformations changes in small proteins. Together, the various studies within this project will provide algorithms and a roadmap for the effective use of ICMD. We will lay the basis for integration of these algorithms with the widely used MD software package NAMD for wider dissemination.

描述（由申请人提供）：分子动力学（MD）模拟是结构生物学的强大计算工具，广泛用于理解蛋白质的构象变化和肽的折叠。但是，使用笛卡尔动力学模型的MD模拟受到大蛋白的数十纳秒含量的总模拟时间尺度的限制。另一方面，生物过程需要微秒的模拟时间。已经开发了内部坐标分子动力学（ICMD）算法，以实现更大的模拟时间段，并在长时间尺度模拟中显示出巨大的希望。尽管有希望，ICMD技术在很大程度上取得了很大的进步，这在很大程度上是由于内部坐标模型的其他数学复杂性。我们建议通过ICMD算法解决和解决关键的瓶颈问题。我们建议开发，验证广义的Neimo（Gneimo）ICMD方法，该方法仅冻结键长，键角和键长，以及使用ICMD方法使用模型固定策略进行更广泛的构象搜索。我们还建议表征ICMD算法在应用中的性能，例如1）维持天然蛋白质结构，2）近乎天然同源性结构模型的细化，3）α螺旋螺旋和β螺旋蛋白肽的折叠以及4）小蛋白质中的结构变化。该项目中的各种研究将提供算法和有效使用ICMD的路线图。我们将为将这些算法与广泛使用的MD软件包NAMD集成以进行更广泛的传播奠定基础。