DEVELOPMENT OF THEORETICAL METHODS FOR STUDYING BIOLOGICAL MACROMOLECULES

新的理论技术正在发展和特点。 这些工作通常与软件开发相结合， 包括对新想法的系统测试和评估。 这 发展是由当前的需要和利益驱动的。 具体 项目包括： - Ewald求和净电荷修正的发展 - 结合能预测方法的评价 - REPLICA/PATH法测定反应的发展 复杂系统中的路径 - 量子力学/分子模型结合的发展 (QM/MM）电势和算法（MM电荷的高斯模糊） - 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 - 柔性约束MD技术的发展 - 分子动力学模拟的辛方法 - 合理药物设计：CHARMM的形状描述工具 - 构象的局部增强采样（LES）测试 搜索 尽管通常被使用的许多参数集和模型 可提供的是精确模拟所需的质量， 大分子系统，仍然需要权衡相对 这些集的优点，为特定类型的系统研究中， MGS 还有水的处理等众多细节 和远距离静电。正在进行的项目包括： - 可极化和柔性水模式的开发和使用 - 大分子中长程相互作用的近似 使用Ewald和和粒子网格的变体进行模拟 埃瓦尔德方法 - 隐式和显式水模型的评价和比较 用于模拟检测蛋白质的水合作用 - 参数集的评价

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 Ewald summation net-charge corrections - Evaluation of binding energy prediction methods - Development of the REPLICA/PATH method for determining reaction paths in complex systems using simulated annealing - Development of combined Quantum Mechanical/Molecular Modeling (QM/MM) potentials and algorithms (gaussian blur of MM charges) - Evaluation of alternate treatments of QM/MM interfaces - Development of grid-based density functional methods for QM/MM modeling - Development of flexible constraints MD techniques - Symplectic methods for molecular dynamics simulations - Rational drug design: shape descriptor facility for CHARMM - Testing of Locally Enhanced Sampling (LES) for conformational searching 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