New solvent models, sampling methods and maintenance of Amber software

说明(申请人提供)：本提案响应PAR-11-028，软件的持续开发和维护：该计划的目标是支持现有软件的持续开发、维护、测试和评估。琥珀是一个流行的软件包，授权给800多个学术和工业机构，用于模拟分子体系的结构、热力学和动力学性质。由Pi Carlos Simmerling在石溪开发的广受欢迎的琥珀ff99Sb力场被引用了885次。西默林小组是负责琥珀维护和开发的六个学术小组之一。使用Amber和其他软件包的计算分子动力学模拟已经成为了解生物分子机制和发现抑制生物分子的药物的实验研究的重要对应物。广受欢迎的虚拟筛选程序名为Dock，直接与Amber交互。这里提出的软件改进的一个目标是减少开发新药所需的时间。我们在这里为琥珀提出了新的发展，以满足该领域最紧迫的需求。目标1，溶剂化：我们将包括改进的溶剂化模型：(A)SEA半显式水模型和(B)新的广义Born模型。目标2，采样：我们将增加快速和有针对性的采样方法：(A)通用工具哈密顿交换和热复制交换分子动力学的变体，(B)新的有限数据建模方法，它在稀疏和噪声数据下采样构象；(C)用于采样环构象的非常快速的动力学环闭合和约束环闭合方法，以及(D)限制和过渡法，它计算生物分子两种不同构象之间的自由能差。我们将把我们最近开发的算法整合到琥珀生产代码中进行分发，并使用CUDA将代码移植到最近开发的琥珀GPU版本。

DESCRIPTION (provided by applicant): This proposal responds to PAR-11-028, Continued Development and Maintenance of Software: The goal of this program is to support the continued development, maintenance, testing and evaluation of existing software. Amber is a popular software package, licensed to over 800 academic and industry institutions, for simulating the structural, thermodynamic and kinetic properties of molecular systems. There are 885 citations to the popular Amber ff99SB force field, developed at Stony Brook by PI Carlos Simmerling. The Simmerling group is one of the six academic groups responsible for Amber maintenance and development. Computational Molecular Dynamics simulations using Amber and other software packages have become essential counterparts to experimental research for understanding the mechanisms of biomolecules, and for discovering drugs to inhibit them. The popular virtual screening program called DOCK interfaces directly with Amber. One goal of the software improvements proposed here is to reduce the time it takes to develop new drugs. We propose here new developments for Amber, addressing the most pressing needs of the field. Aim 1, Solvation: We will incorporate improved solvation models: (a) the SEA semi-explicit water model and (b) a new Generalized Born model. Aim 2, Sampling: We will add fast and targeted sampling methods: (a) variants of the general tools Hamiltonian exchange and thermal Replica Exchange Molecular Dynamics, (b) the new Modeling with Limited Data method, which samples conformations subject to sparse and noisy data; (c) the very fast Kinetic-Loop-Closure and Constrained-Loop-Closure methods for sampling loop conformations, and (d) the Confine and Transition method, which computes free- energy differences between two different conformations of a biomolecule. We will incorporate our recently developed algorithms into the Amber production code for distribution, and port the codes to the recently developed GPU version of Amber using CUDA.