AMBER force field consortium: a coherent biomolecular simulation platform

分子模拟在生物化学和生物物理科学中发挥着重要作用。预付款 已经实现了对日益复杂的系统进行广泛的模拟。进一步推进这些 进展，这组调查人员建议建立一个财团来开发参数和 模拟方法学是分子模拟平台基础的一部分。建议数 该联盟聚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，以 推动部队实地攻坚再上新台阶。这些调查人员做出了重大贡献 ：o开发琥珀模拟程序包和力场参数，并进行了 过去的重大合作，这从作者之间的许多联合出版物中可见一斑。 这项提议的一个关键重点是不仅要为以下领域开发通用、可靠和广泛适用的力场 蛋白质、核酸和类药物分子，但要通过彻底的测试和 与其他可用的方法和力场进行比较。目前，在以下方面做出的选择 模型(极化、电荷模型、溶剂表示)仍然是活跃的研究课题。这项建议 涉及面广，将调查多种方法，从Next的开发 生成通用可极化力场到专门设计的模型，以利用 连续溶剂。从组建的团队来看，在蛋白质和蛋白质模拟方面有相当多的专业知识 核酸是显而易见的，这将有助于指导努力向前发展。该财团的一个主要目标是 进一步加强密切合作，使创意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)基于以下条件的完全可极化模型 将发展Thole的偏振方案。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)一种新的隐式 将开发包括固定和动态溶剂和溶质极化率的溶剂模型；3) 将进一步开发加性和联合原子模型，以开发一种混合模型，该模型 结合了关键偏振效应，其计算成本与典型固定点相当 电荷模型和精炼侧链参数以改进能量的表示 表面；4)发展一般的琥珀力场(GAFF)模型将允许更准确 用改进的方法表示与生物大分子相互作用的多组类药物分子 附加的和可极化的力场；5)模拟方法和相关参数 通过与实验的直接比较，严格审查和批判性评估。

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.