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（由申请人提供）：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，允许对日益复杂的系统进行广泛的模拟。随着这些进步的发展，这组研究人员建议建立一个联盟，以开发参数和模拟方法，这些方法是分子模拟平台基础的一部分。拟议中的财团汇集了一群年轻的研究人员，即加州大学洛杉矶分校的Kollman实验室的所有前成员，以将“琥珀色”的野外努力推向新的水平。这些调查人员做出了重大贡献：o琥珀色模拟包和力场参数的开发，并在过去进行了重要的合作，这是作者中许多联合出版物都可以明显看出的。该建议的重点不仅是为蛋白质，核酸和药物样分子开发一般，可靠且广泛适用的力场，而且还通过彻底的测试和比较与其他可用方法和力场进行验证。目前，根据模型（极化，电荷模型，溶剂表示）做出的选择仍然是积极的研究问题。该提议正在广泛地进行，因为将研究多种方法，从下一代通用可极化力场的开发到专门设计用于利用连续溶剂的模型。从团队组装的蛋白质和核酸模拟中的大量专业知识很明显，这将有助于指导前进的努力。该财团的一个关键目标是进一步增强密切的合作，该协作可以更快地测试和审查想法。拟议的工作在以下领域进行了广泛分类。 1）将开发基于Thole的极化方案的完全极化模型。预计这种力场将改善与二价离子，药物和环境相互作用的生物分子的表示。 2）将开发一种新的隐式溶剂模型，以结合固定和动态溶剂和溶质极化性； 3）将追求进一步开发添加剂和联合原子模型，以开发一种混合模型，该模型将关键的极化效应与典型固定点电荷模型的可比计算成本结合在一起，并完善侧链参数以改善能量表面的表示； 4）一般琥珀色力场（GAFF）模型的发展将使与改善的加性和极化力场所代表的生物分子相互作用的不同药物样分子相互作用。 5）模拟方法和相关参数将通过与实验直接比较进行大力审查并进行严格评估。