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: 7497004
• 负责人: YONG DUAN
• 金额: $ 55.52万
• 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 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7497004
• 关键词: Adoption; Algorithms; Amber; Amino Acids; Area; Binding; Biochemical; Biological; Biological Models; Carbon; Charge; Chemicals; Collaborations; Communities; Complement; Complex; Computers; Data; Development; Electronics; Electrostatics; Environment; Equilibrium; Evaluation; Event; Evolution; Foundations; Goals; Growth; Hybrids; Hydrogen Bonding; Ions; Joints; Learning; Ligands; Metals; Methodology; Methods; Modeling; Molecular; Nucleic Acids; Numbers; Object Attachment; Peptides; Pharmaceutical Preparations; Pharmacologic Substance; Play; Population; Protein Dynamics; Proteins; Publications; Purpose; RNA; Range; Research; Research Personnel; Role; Sampling; Scanning; Scheme; Science; Series; Set protein; Side; Solvents; Structure; Surface; System; Testing; Time; Torsion; Update; Validation; Vertebral column; Work; base; cost; density; design; dipole moment; environmental change; experience; improved; insight; member; next generation; programs; protein folding; research study; response; simulation; size; solute

Molecular simulations have played important roles in biochemical and biophysical sciences. Advances have been made that have allowed extensive simulations of increasingly complex systems. Furthering these advances, this group of investigators proposes to establish a consortium to develop parameters and simulation methodologies that are part of the foundation of molecular simulation platform. The proposed consortia brings together a group of young researchers, all former members of the Kollman lab at UCSF, to push the "Amber" force field efforts to the next level. These investigators have made significant contributions :o the development of both Amber simulation package and the force field parameters and have undertaken significant collaboration in the past which is evident by many joint publications among the authors. A key focus of this proposal 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, ranging from development of next generation general-purpose polarizable force field to models specifically designed to take advantage of ontinuum solvent. From the team assembled, considerable expertise in the simulation of proteins and nucleic acids is evident which will help guide the efforts forward. A key objective of the consortium is to further enhance the close collaboration that allows ideas to be tested and vetted much more quickly. The proposed work is broadly categorized in the following areas. 1) A fully polarizable model based on Thole's scheme of polarization will be developed. Such a force field is expected to improve the representation of biomolecules interacting with divalent ions, drugs and the environment; 2) A new implicit solvent model will be developed to incorporate both fixed and dynamic solvent and solute polarizability; 3) Further development of additive and united-atom models will be pursued to develop a hybrid model that incorporates the key polarization effect with a comparable computational cost to that of typical fixed point charge models and to refine the side chain parameters for an improved representation of the energetic surface; 4) Development of the general Amber force field (GAFF) model will allow more accurate representation of diverse sets of drug-like molecules interacting with biomolecules represented by improved additive and polarizable force fields; 5) The simulation methodology and the associated parameters will be vigorously scrutinized and critically assessed through direct comparisons with experiments.

分子模拟在生物化学和生物物理科学中发挥着重要作用。进展 已经允许对日益复杂的系统进行广泛的模拟。进一步推进这些 随着进展，这组研究人员提议建立一个联盟来开发参数和 模拟方法是分子模拟平台基础的一部分。拟议的 该联盟汇集了一群年轻的研究人员，他们都是加州大学旧金山分校科尔曼实验室的前成员， 将“琥珀”力场的努力推向新的高度。这些研究者做出了重大贡献 :o 开发 Amber 模拟包和力场参数并已进行 作者之间的许多联合出版物证明了过去的重要合作。 该提案的一个重点不仅是开发通用的、可靠的和广泛适用的力场 蛋白质、核酸和类药物分子，但要通过彻底的测试和验证来验证力场 与其他可用方法和力场的比较。目前，要做出的选择是 模型（极化、电荷模型、溶剂表示）仍然是活跃的研究问题。这个提议 影响广泛，因为将研究多种方法，从下一步的开发 生成通用极化力场到专门设计的模型，以利用 连续溶剂。组建的团队在蛋白质模拟和 核酸是显而易见的，这将有助于指导工作的进展。该联盟的一个主要目标是 进一步加强密切合作，使想法能够更快地得到测试和审查。 拟议的工作大致分为以下几个领域。 1）基于的完全极化模型 托尔的极化方案将会得到发展。这样的力场有望改善 生物分子与二价离子、药物和环境相互作用的表示； 2）新的隐式 将开发溶剂模型以纳入固定和动态溶剂以及溶质的极化率； 3） 将进一步开发增性模型和联合原子模型，以开发一种混合模型 结合了关键的偏振效应，其计算成本与典型的定点计算成本相当 电荷模型并细化侧链参数以改进能量的表示 表面; 4）通用琥珀力场（GAFF）模型的开发将使得更准确 与生物分子相互作用的不同组类药物分子的表示，以改进的表示 加法力场和极化力场； 5) 模拟方法和相关参数将是 通过与实验的直接比较进行严格审查和严格评估。