Multi-scaled Modeling of Electrostatic and Polarization Effects in Biomolecules

生物分子静电和极化效应的多尺度建模

• 批准号: 10000166
• 负责人: RAY LUO
• 金额: $ 39.25万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10000166
• 关键词: Address; Area; Charge; Communities; Computer Models; Disease; Drug Design; Electrostatics; Event; Gaussian model; Grain; Knowledge Discovery; Medical; Methods; Modeling; Molecular; Phase; Physics; Play; Process; Role; Solvents; Structure; System; base; computer studies; computerized tools; density; experimental study; insight; multi-scale modeling; novel; simulation; tool

Project Summary Physics-based atomistic simulations of biomolecules offer a range of testable observables, providing critical mechanistic insights that are largely inaccessible to experiment. However challenging processes, such as order-disorder transitions, ionic interactions, and interface events near biomembrane, are difficult to model quantitatively with existing approaches. The difficulty comes from the requirement of accurate modeling of electrostatic and polarization effects in different structural states and different solvent phases. This is not easily achievable if we demand that our atomistic model is efficient enough for typical molecular processes. Our central hypothesis to address the accuracy issue is that biomolecules in different solvent phases and in different structural states can only be modeled with satisfactory transferability within polarizable electrostatics frameworks. In a major shift from existing approaches, we are exploring a polarizable Gaussian Multipole model, where all charges and multipoles are represented by Gaussian densities instead of classical points. On the other hand polarization treatments invariably reduce simulation efficiency, leading to a more pronounced efficiency issue. Thus a second major difference from existing approaches is our concurrent focus on efficiency based on a multi-scaled framework with all-atom polarizable, coarse-grained polarizable, and continuum polarizable models, which are consistent with each other. This allows them to be more easily interfaced in multi-scaled simulation methods. Our plan can be summarized in the following four areas. First we will develop a novel polarizable force field. Second we will develop and extend continuum polarizable solvent models consistent with the new polarizable force field. Third a coarse-grained polarizable force field will be developed. Finally, we will continue to apply our computational models and tools to study interesting biomedical problems that best demonstrate the potentials of the new models. We will concurrently disseminate the new models and tools to positively impact the biomedical community. Through these concerned efforts, we will offer the community a multi-scaled set of computer models to model biomolecular electrostatics and polarization for a range of interesting systems of biomedical importance.

项目摘要 基于物理学的生物分子的原子模拟提供了一系列可可观察的物品，提供了关键 机械洞察力在很大程度上无法实验。但是具有挑战性的过程，例如 生物膜附近的订单界限过渡，离子相互作用和界面事件很难建模 定量使用现有方法。困难来自于准确建模的要求 不同结构状态和不同溶剂相的静电和极化效应。这不容易 如果我们要求我们的原子模型足以在典型的分子过程中有效，则可以实现。我们的 解决准确性问题的中心假设是不同溶剂阶段的生物分子和 不同的结构状态只能以令人满意的可传递性在两极分化的静电中进行建模 框架。在与现有方法的重大转变中，我们正在探索可极化的高斯多极 模型，其中所有电荷和多物都由高斯密度而不是经典点表示。在 另一方面极化处理总是降低模拟效率，导致更明显的 效率问题。因此，与现有方法的第二个主要区别是我们同时关注效率 基于一个多尺度的框架，其全原子可极化，可粗两个极化和连续性 可极化的模型，它们彼此一致。这使他们可以更容易地将 多尺度仿真方法。我们的计划可以在以下四个领域中进行总结。首先我们会发展 一个新颖的极化力场。第二，我们将开发和扩展连续极化溶剂模型 与新的极化力场一致。第三将开发出粗粒极化的力场。 最后，我们将继续应用我们的计算模型和工具来研究有趣的生物医学问题 最好证明新模型的潜力。我们将同时传播新模型，并 积极影响生物医学界的工具。通过这些有关的努力，我们将提供 社区一组多尺度的计算机模型，以建模生物分子静电和极化 一系列有趣的生物医学重要体系。