DEVELOPMENT OF THEORETICAL METHODS FOR STUDYING BIOLOGICAL MACROMOLECULES

生物大分子研究理论方法的发展

• 批准号: 2571577
• 负责人: B R BROOKS
• 金额: --
• 依托单位: CENTER FOR INFORMATION TECHNOLOGY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2571577
• 关键词: chemical models; chemical structure; computer program /software; computer simulation; drug design /synthesis /production; intermolecular interaction; macromolecule; mathematical model; model design /development; molecular dynamics; physical model; protein structure; quantum chemistry

New theoretical techniques are being developed and characterized. These efforts are usually coupled with software development, and involve the systematic testing and evaluation of new ideas. This development is driven by current needs and interests. Specific projects include: - Development of Langevin piston methods for NPT simulation of periodic systems and for stochastic boundary MD simulations - Development of combined quantum mechanical/Molecular modeling (QM/MM) potentials and algorithms for use in molecular dynamics simulations - Evaluation of alternate treatments of QM/MM interfaces - Development of grid-based density functional methods for QM/MM modeling - Evaluation and development of techniques to rapidly estimate protein- ligand binding affinities - Development of the REPLICA/PATH method for determining reaction paths in complex systems using simulate annealing - Development of flexible constraints MD techniques - Symplectic methods for molecular dynamics simulations - Development of constant pressure stochastic boundary methods - Rational drug design: shape descriptor facility for CHARMM - Prediction of sidechain placement, insertions, and deletions in homology modeling - Analysis of experimental data by the maximum entropy method (MEM) Although many of the parameter sets and models that are generally available are of the quality required for accurate simulation of macromolecular systems, there remains the need to weigh the relative merits of these sets for the specific types of systems studied in the MGS. There are also numerous details such as the treatment of water and long-range electrostatics. Ongoing projects include: - Development and use of a polarizable and flexible water model - Approximation of long-range interactions in macromolecular simulation using variants of the Ewald sum and the particle mesh Ewald methods - Evaluation and comparison of implicit and explicit water models for simulations examining the hydration of proteins - Evaluation of parameter sets

新的理论技术正在发展和特点。 这些 这些工作通常与软件开发相结合， 系统测试和评估新想法。 这种发展是由 当前的需求和利益。 具体项目包括： - Langevin活塞法在NPT周期性流场数值模拟中的应用 系统以及实现 随机边界MD模拟 - 结合量子力学/分子模拟的发展 (QM/MM）势和算法在分子动力学中的应用 模拟 - QM/MM界面替代治疗的评价 - 基于网格的QM/MM密度泛函方法的发展 建模 - 评价和开发快速估计蛋白质的技术- 配体 结合亲和力 - 确定反应路径的REPLICA/PATH方法的发展 在使用模拟退火的复杂系统中 - 柔性约束MD技术的发展 - 分子动力学模拟的辛方法 - 定压随机边界方法的发展 - 合理药物设计：CHARMM的形状描述工具 - 预测侧链的位置，插入，和缺失， 同源性 建模 - 用最大熵方法（MEM）分析实验数据 尽管通常可用的许多参数集和模型 具有精确模拟大分子所需的质量 尽管如此，仍然需要权衡这些系统的相对优点， 对于MGS中研究的特定类型的系统。 也有 许多细节，如水的处理和远程 静电学 正在进行的项目包括： - 可极化和柔性水模式的开发和使用 - 大分子模拟中长程相互作用的近似 使用Ewald和和粒子网格Ewald方法的变体 - 隐式和显式水模型的评价和比较 研究蛋白质水合作用的模拟 - 参数集的评价