AMBER force field consortium: a coherent biomolecular simulation platform

项目摘要 分子模拟在生物化学和生物物理科学中发挥着重要作用。 已经取得的进展使得对日益复杂的 具有不断增长的时间和规模的系统。琥珀部队战地联盟是一支由 在质量管理计算等领域具有高度互补性的调查人员， 可极化和固定的带电力场，以及溶剂模型，以验证力场。这 Synergy帮助统一和支持了琥珀部队的实地开发。的长期目标 该联盟将开发能够复制生物结构、动力学和 相互作用，而不会牺牲生物学上所需的计算效率 相关的时间尺度。随着琥珀可极化力场ff12poll的释放，该财团 在精确表示蛋白质的高能表面方面取得了重大进展 和核酸。为了进一步推动这些进展，琥珀部队战地联盟提议 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了一个新的水平。 该联盟的一个重点是不仅开发出通用的、可靠的和广泛适用的 蛋白质、核酸和类药物分子的力场，但通过 与其他可用的方法和力场进行了彻底的测试和比较。目前， 根据模型(极化、电荷模型、溶剂表示)进行的选择如下 仍在研究中的问题。这项提议影响广泛，因为多种方法将 被调查。财团的一个主要目标是进一步加强密切合作。 这使得创意能够更快地得到测试和调查。 拟议的工作大致分为以下几个领域。1)开发一个 可极化的一般琥珀力场模型将允许更准确地表示不同的 由极化力表示的与生物分子相互作用的类药物分子组 2)显式考虑原子的连续介质溶剂模型的发展 极化将扩大可极化力场的适用范围，使高效 和精确的自由能计算；3)模拟方法和相关的 参数将通过直接比较严格审查和严格评估 在一组广泛的模型系统上进行实验。

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.