GNEIMO: Generalized Internal Coordinate Molecular Dynamics Methods

GNEIMO：广义内坐标分子动力学方法

• 批准号: 8139915
• 负责人: Nagarajan Vaidehi
• 金额: $ 29.53万
• 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 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8139915
• 关键词: Address; Algorithms; Biological Process; California; Communities; Computer software; Development; Drug Formulations; Equation; Foundations; Freedom; Freezing; Frequencies; Future; Generations; Graph; Homology Modeling; Illinois; Length; Letters; Methods; Modeling; Molecular Conformation; Motion; Neurotoxins; Peptides; Performance; Plague; Principal Investigator; Process; Protein Structure Initiative; Proteins; Publishing; Qualifying; 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）模拟是结构生物学中强大的计算工具，广泛用于理解蛋白质的构象变化和肽的折叠。然而，使用笛卡尔动力学模型的 MD 模拟受到大蛋白质的总模拟时间尺度为数十纳秒的限制。另一方面，生物过程需要微秒的模拟时间。内坐标分子动力学 (ICMD) 算法的开发是为了实现更大的模拟时间步长，并且它们在长时间尺度模拟中显示出巨大的前景。尽管 ICMD 技术前景广阔，但其进展甚微，这在很大程度上是由于内部坐标模型的额外数学复杂性。我们建议用 ICMD 算法来解决和解决关键瓶颈问题。我们建议开发、验证广义 NEIMO (GNEIMO) ICMD 方法，该方法允许仅冻结键长、键角和键长，并使用 ICMD 方法使用模型粗化策略进行更广泛的构象搜索。我们还建议表征 ICMD 算法在以下应用中的性能：1）维持天然蛋白质结构，2）细化近乎天然的同源结构模型，3）α螺旋和β发夹肽的折叠以及4）小蛋白质的构象变化。该项目中的各种研究共同将为 ICMD 的有效使用提供算法和路线图。我们将为这些算法与广泛使用的 MD 软件包 NAMD 的集成奠定基础，以实现更广泛的传播。

项目成果

GneimoSim: a modular internal coordinates molecular dynamics simulation package.

GneimoSim：模块化内坐标分子动力学模拟软件包。

• DOI: 10.1002/jcc.23743
• 发表时间: 2014
• 期刊: Journal of computational chemistry
• 影响因子: 3
• 作者: Larsen,AdrienB;Wagner,JeffreyR;Kandel,Saugat;Salomon-Ferrer,Romelia;Vaidehi,Nagarajan;Jain,Abhinandan
• 通讯作者: Jain,Abhinandan

Advanced techniques for constrained internal coordinate molecular dynamics.

• DOI: 10.1002/jcc.23200
• 发表时间: 2013-04-30
• 期刊: JOURNAL OF COMPUTATIONAL CHEMISTRY
• 影响因子: 3
• 作者: Wagner, Jeffrey R.;Balaraman, Gouthaman S.;Niesen, Michiel J. M.;Larsen, Adrien B.;Jain, Abhinandan;Vaidehi, Nagarajan
• 通讯作者: Vaidehi, Nagarajan

Structure refinement of protein low resolution models using the GNEIMO constrained dynamics method.

• DOI: 10.1021/jp209657n
• 发表时间: 2012-03-01
• 期刊: JOURNAL OF PHYSICAL CHEMISTRY B
• 影响因子: 3.3
• 作者: Park, In-Hee;Gangupomu, Vamshi;Wagner, Jeffrey;Jain, Abhinandan;Vaidehi, Nagarajan
• 通讯作者: Vaidehi, Nagarajan

Internal coordinate molecular dynamics: a foundation for multiscale dynamics.

• DOI: 10.1021/jp509136y
• 发表时间: 2015-01-29
• 期刊: The journal of physical chemistry. B
• 作者: Vaidehi N;Jain A
• 通讯作者: Jain A

Fixman compensating potential for general branched molecules.

Fixman 补偿一般支链分子的潜力。

• DOI: 10.1063/1.4851315
• 发表时间: 2013
• 期刊: The Journal of chemical physics
• 作者: Jain,Abhinandan;Kandel,Saugat;Wagner,Jeffrey;Larsen,Adrien;Vaidehi,Nagarajan
• 通讯作者: Vaidehi,Nagarajan