DYNAMICAL SIMULATIONS OF KINKED DNA AND CRYSTALLOGRAPHIC REFINEMENT BY SIMULATE

扭结 DNA 的动态模拟和通过模拟进行的晶体细化

• 批准号: 7723102
• 负责人: JOHN M ROSENBERG
• 金额: $ 0.05万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7723102
• 关键词: Amino Acids; Basic Amino Acids; Biochemical; Charge; Complex; Computer Retrieval of Information on Scientific Projects Database; Cystine; Development; Electrostatics; Funding; Glutamic Acid; Grant; Hybrids; Institution; Macromolecular Complexes; Methods; Microscopic; Modeling; Numbers; Proteins; Range; Research; Research Personnel; Resources; Side; Simulate; Site; Solvents; Source; Staging; System; Thermodynamics; Titrations; United States National Institutes of Health; Weight; abstracting; base; improved; models and simulation; molecular dynamics; simulation

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. Keywords: Molecular Dynamics, Monte Carlo, Weighted Histograms, constant pH simulation, pKa calculation Abstract: It is necessary to properly treat titratable groups, such as acidic or basic amino acid residues, during the course of a molecular dynamics simulation, especially since fluctuations in titration states are expected to be correlated with other configurational parameters. This is especially challenging in macromolecular complexes such as protein-DNA complexes, where many titratable and/or charged groups are a significant distance from bulk solvent. We are developing a hybrid Molecular Dynamics/Monte Carlo-Multiple Histogram (MD/MC-WHAM) method for constant pH simulations and pKa calculations. A summary of the features of our combined MC/MC-WHAM approach is as follows: 1) Explicit solvent is used, improving the electrostatic modeling. The simulation force field is based on the microscopic Amber8 Force Field(1,2), which includes Ewald long-range electrostatics, and optional polarizability 2) Each titratable site is modeled in detail with discrete microstates. 3) One simulation cycle consists of an MD sub-cycle and an MC sub-cycle. The MD enforces constant N,P,T and the MC enforces constant pH. Together both sub-cycles model a true biochemical ensemble, constant N,P,T and pH. This facilitates modeling of correlations between the titration states at multiple sites as well as between titration states and configuration states. 4) WHAM(5,6) histogram methods facilitate the calculation of a full range of thermodynamic parameters, including titration curves and pKa values. This proposal is for the next stages of development, which are to: 1) Complete determination of the force field correction number for Cystine 2) Determine statistical requirements (# of snapshots) for given levels of precision 3) Investigate system with two titratable sites to verify that appropriate interactions are being simulated 4) Determine the correction term for a second amino acid side chain (Glutamic acid)

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。 关键字：分子动力学，蒙特卡洛，加权直方图，恒定pH模拟，PKA计算 抽象的： 有必要正确处理可滴定组，例如酸性或 在分子动力学过程中，碱性氨基酸残基 模拟，特别是因为预计滴定状态的波动 与其他配置参数相关。 尤其是 在大分子复合物（例如蛋白质-DNA复合物）中挑战， 许多可滴定和/或充电组与 散装溶剂。 我们正在开发混合分子动力学/蒙特 用于恒定pH模拟的CARLO-MULTIPE-PINEMAGING（MD/MC-WAM）方法 和PKA计算。 我们组合的MC/MC-WAM方法的特征摘要是 以下内容： 1）使用显式溶剂，改善静电建模。 模拟力场基于微观Amber8力 字段（1,2），包括埃瓦尔德（Ewald）长距离静电和可选 极化性 2）每个可滴定站点详细建模 微骨。 3）一个模拟周期由MD子周期和MC组成 子周期。 MD强制执行常数N，P，T和MC执行常数pH。 两个子循环一起建模真正的生化合奏，常数n，p，t 和ph。 这有助于滴定之间的相关性建模 在多个站点以及滴定状态之间的状态和 配置状态。 4）WHAM（5,6）直方图方法有助于计算完整 热力学参数范围，包括滴定曲线和PKA 值。 该提议是针对发展的下一个阶段，该阶段是： 1）完全确定力场校正号 胱氨酸 2）确定给定的统计要求（快照＃） 精度水平 3）使用两个可滴定站点调查系统，以验证 正在模拟适当的互动 4）确定第二个氨基酸侧链的校正项 （谷氨酸）