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: 7321186
• 负责人: YONG DUAN
• 金额: $ 62.31万
• 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/7321186
• 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

DESCRIPTION (provided by applicant): 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 continuum 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.

描述（申请人提供）：分子模拟在生物化学和生物物理科学中发挥着重要作用。已经取得的进展使得对日益复杂的系统进行广泛的模拟成为可能。进一步推进这些进展，这组研究人员建议建立一个联盟来开发参数和模拟方法，这是分子模拟平台基础的一部分。拟议中的联盟将一群年轻的研究人员聚集在一起，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”力场的努力推向一个新的水平。这些研究人员在Amber模拟包和力场参数的开发方面做出了重大贡献，并在过去进行了重要的合作，这在作者之间的许多联合出版物中是显而易见的。本方案的重点在于，不仅要为蛋白质、核酸和类药物分子开发通用的、可靠的、广泛适用的力场，而且要通过全面的测试和与其他现有方法和力场的比较来验证该力场。目前，在模型（极化、电荷模型、溶剂表征）方面的选择仍是活跃的研究问题。该建议具有广泛的意义，因为将研究多种方法，从开发下一代通用极化力场到专门设计利用连续介质溶剂的模型。从组建的团队来看，在蛋白质和核酸模拟方面的相当多的专业知识是显而易见的，这将有助于指导未来的努力。该联盟的一个关键目标是进一步加强密切合作，以便更快地对想法进行测试和审查。建议的工作大致分为以下几方面。1)建立基于Thole极化格式的全极化模型。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征；2)建立一个包含固定和动态溶剂和溶质极化率的隐式溶剂模型；3)将进一步发展可加和联合原子模型，以建立一个混合模型，该混合模型包含关键极化效应，其计算成本与典型的定点电荷模型相当，并改进侧链参数，以改进含能表面的表示；4)通用琥珀力场（GAFF）模型的发展将允许更准确地表示各种药物样分子与生物分子相互作用的集合，通过改进的加法和极化力场来表示；5)模拟方法和相关参数将通过与实验的直接比较进行严格审查和严格评估。