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。 已经取得的进展已经允许对日益复杂的 随着时间和规模的增长，琥珀力场联盟是一个 调查人员在QM计算， 可极化和固定带电力场以及溶剂模型，以进行力场验证。这 协同作用有助于统一和实现琥珀部队的外地发展。的长期目标 该联盟将开发可以复制生物结构，动力学和 相互作用，而不牺牲必要的计算效率，达到生物学 相关时间表。随着琥珀极化力场ff 12 pol的发布， 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。为了进一步推进这些进展，琥珀力场联合体建议， 开发参数和模拟方法，作为分子基础的一部分， 仿真平台，以推动 琥珀 把外勤工作提升到一个新的水平 该联盟的一个重点是不仅要开发通用、可靠和广泛适用的 力场的蛋白质，核酸和药物样分子，但要验证力场通过 全面测试并与其他可用方法和力场进行比较。目前该 根据模型（极化、电荷模型、溶剂表示）做出的选择是 仍然是活跃的研究问题。这一建议具有广泛意义，因为多种方法将 追究该联盟的一个主要目标是进一步加强与 这使得想法能够更快地被测试和调查。 拟议的工作大致分为以下几个方面。1)发展 极化一般琥珀力场模型将允许更准确地表示不同的 与生物分子相互作用的药物样分子组，由极化力表示 2）发展连续溶剂模型，明确考虑原子 极化将扩大可极化力场的适用范围， 和准确的自由能计算; 3）模拟方法和相关的 参数将通过直接比较进行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.