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.

项目摘要 分子模拟在生化和生物物理科学中起着重要作用。 已经取得了进步，允许对日益复杂的广泛模拟 具有增长时间和尺寸尺度的系统。 Amber Force Field Consortium是一个团队 在QM计算方面具有高度互补专业知识的研究人员， 可极化和固定带电的力场和溶剂模型，以强制场验证。这 Synergy帮助统一和实现了Amber Force Field Field的发展。长期目标 该财团是为了发展可以重现生物结构，动力学和 相互作用而无需牺牲生物学上所需的计算效率 相关时间尺度。随着琥珀极化力场FF12Pol的释放，该财团 已经大大涉及准确代表蛋白质的能量表面 和核酸。进一步进步，琥珀色力场联盟提议 开发参数和仿真方法，这些方法是分子基础的一部分 仿真平台将琥珀色的现场工作推向新的水平。 该财团的重点不仅是发展一般，可靠且广泛适用 蛋白质，核酸和药物样分子的力场，但通过 与其他可用方法和力场进行彻底的测试和比较。目前， 根据模型（极化，电荷模型，溶剂表示）做出的选择是 仍然活跃的研究问题。该提议正在广泛了解，以至于多种方法将 被调查。该财团的关键目标是进一步增强密切合作 这样可以更快地测试和调查想法。 拟议的工作在以下领域进行了广泛分类。 1）发展 可极化的一般琥珀色力场模型将允许更准确地表示多种 与可极化力代表的生物分子相互作用的药物样分子集 字段； 2）开发具有明确考虑原子的连续溶剂模型 极化将扩展可极化力场的适用性范围，并有效 和准确的自由能计算； 3）模拟方法和相关的 参数将通过与直接比较进行严格审查并进行严格评估 在一组广泛的模型系统上进行实验。