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。进展 已经允许对日益复杂的系统进行广泛的模拟。促进这些 为了取得进展，这组研究人员建议建立一个联合会，以制定参数， 模拟方法是分子模拟平台基础的一部分。拟议 财团汇集了一群年轻的研究人员，所有的前成员科尔曼实验室在加州大学旧金山分校， 把“琥珀”力场的工作推进到一个新的水平这些研究人员做出了重大贡献 o制定了琥珀模拟包和力场参数，并已着手 过去的重要合作，作者之间的许多联合出版物证明了这一点。 这项建议的一个关键重点是，不仅要发展通用、可靠和广泛适用的力场， 蛋白质，核酸和药物样分子，但要通过彻底的测试来验证力场， 与其他可用的方法和力场进行比较。目前，在这方面作出的选择 模型（极化，电荷模型，溶剂表示）仍然是活跃的研究问题。这项建议 将研究多种方法，从开发下一个 生成通用的可极化力场，以专门设计的模型， 连续溶剂从团队组装，相当专业的模拟蛋白质和 核酸是显而易见的，这将有助于指导努力向前迈进。该联盟的一个主要目标是 进一步加强密切合作，使想法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方面。1)一个完全可极化的模型， Thole的偏振方案将得到发展。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示; 2）一个新的隐式 将开发溶剂模型，以结合固定和动态溶剂和溶质极化率; 3） 将进一步发展添加剂和联合原子模型，以开发一种混合模型， 将关键极化效应与典型固定点的计算成本相比较 电荷模型，并完善侧链参数，以改善能量的代表性 4）通用琥珀力场（GAFF）模型的开发将允许更准确的 与生物分子相互作用的不同药物样分子组的表示， 可加性和可极化力场; 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的审查和批判性的评估。

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.