AMBER force field consortium: a coherent biomolecular simulation platform

AMBER 力场联盟：相干生物分子模拟平台

• 批准号: 8632771
• 负责人: Piotr Cieplak
• 金额: $ 55.53万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-28 至 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8632771
• 关键词: Algorithms; Amber; Area; Binding; Biochemical; Biological; Biological Models; Biophysics; Charge; Chemicals; Collaborations; Communities; Complement; Complex; Computer Assisted; Computers; DNA; Data; Derivation procedure; Development; Environment; Evaluation; Event; Evolution; Foundations; Free Energy; Goals; Growth; Ligands; Membrane Proteins; Methodology; Methods; Modeling; Molecular; Nucleic Acids; Peptides; Pharmaceutical Preparations; Pharmacologic Substance; Play; Protein Dynamics; Proteins; RNA; Research; Research Personnel; Role; Sampling; Series; Small RNA; Solid; Solvents; Structure; Surface; System; Testing; Time; Torsion; Validation; Work; biological systems; drug discovery; experience; improved; insight; molecular mechanics; rapid technique; research study; simulation

Project Summary Molecular simulations have played important roles in biochemical and biophysical sciences. Advances have been made that have allowed extensive simulations of increasingly complex systems with growing time and size scales. The Amber force field consortium is a team of investigators with highly complementary expertise in areas ranging from QM calculations, polarizable and fixed charged force fields, and solvent models, to force field validation. This synergy has helped to unify and enable Amber force field development. The long-term goals of this consortium are to develop force fields that can reproduce biological structure, dynamics and interactions without sacrificing the computational efficiency necessary to reach biologically relevant timescales. With the release of Amber polarizable force field ff12pol, the consortium has made significant inroads towards accurately representing the energetic surfaces of proteins and nucleic acids. Furthering these advances, the Amber force field consortium proposes to develop parameters and simulation methodologies that are part of the foundation of molecular simulation platform to push the Amber force field efforts to the next level. A key focus of this consortium is to not only develop general, reliable and widely applicable force fields for proteins, nucleic acids and drug-like molecules, but to validate the force fields via thorough testing and comparison to other available methods and force fields. At present, the choices to make in terms of the model (polarization, charge model, solvent representation) are still active research questions. This proposal is broad-reaching in that multiple approaches will be investigated. A key objective of the consortium is to further enhance the close collaboration that allows ideas to be tested and investigated much more quickly. The proposed work is broadly categorized in the following areas. 1) Development of a polarizable general Amber force field model will allow more accurate representation of diverse sets of drug-like molecules interacting with biomolecules represented by the polarizable force fields; 2) Development of continuum solvent models with explicit consideration of atomic polarization will extend the range of applicability of polarizable force field and enable efficient and accurate free energy calculations; 3) The simulation methodology and the associated parameters will be rigorously scrutinized and critically assessed through direct comparisons with experiments on an extensive set of model systems.

项目概要 分子模拟在生物化学和生物物理科学中发挥着重要作用。 已经取得的进步使得可以对日益复杂的情况进行广泛的模拟 时间和规模不断增长的系统。 Amber 力场联盟是一个由 研究人员在 QM 计算等领域具有高度互补的专业知识， 可极化和固定带电力场以及溶剂模型，以进行力场验证。这 协同作用有助于统一并实现琥珀力场的开发。的长期目标 该联盟将开发能够再现生物结构、动力学和 相互作用而不牺牲达到生物学所需的计算效率 相关的时间尺度。随着Amber极化力场ff12pol的发布，该联盟 在准确表示蛋白质的能量表面方面取得了重大进展 和核酸。为了进一步推动这些进步，琥珀力场联盟提议： 开发作为分子基础的一部分的参数和模拟方法 模拟平台将琥珀力场的努力推向新的水平。 该联盟的重点不仅是开发通用、可靠且广泛适用的 蛋白质、核酸和类药物分子的力场，但要通过以下方式验证力场 与其他可用方法和力场进行彻底测试和比较。目前， 根据模型（极化、电荷模型、溶剂表示）做出的选择是 仍然是活跃的研究问题。该提案影响广泛，因为多种方法将 被调查。该联盟的一个主要目标是进一步加强密切合作 这使得想法能够更快地得到测试和研究。 拟议的工作大致分为以下几个领域。 1) 开发一个 可极化的通用琥珀力场模型将允许更准确地表示不同的 与由极化力表示的生物分子相互作用的一组类药物分子 领域； 2) 明确考虑原子的连续溶剂模型的开发 极化将扩展极化力场的适用范围并实现高效 和准确的自由能计算； 3）模拟方法及相关 参数将通过直接比较进行严格审查和严格评估 对大量模型系统进行实验。