New solvent models, sampling methods and maintenance of Amber software

Amber 软件的新溶剂模型、采样方法和维护

• 批准号: 8558811
• 负责人: CARLOS SIMMERLING
• 金额: $ 29.74万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8558811
• 关键词: Address; Adopted; Agreement; Algorithms; Amber; Basic Science; Biological; Biomedical Research; CASP10 gene; Cereals; Code; Communities; Companions; Complex; Computer Simulation; Computer software; DNA; Data; Data Set; Development; Documentation; Educational workshop; Evolution; Free Energy; Gene Expression; Goals; Hybrids; Industry; Institution; Kinetics; Lead; Licensing; Maintenance; Methodology; Methods; Modeling; Molecular; Molecular Conformation; Neck; Nucleic Acids; Pharmaceutical Preparations; Pharmacotherapy; Production; Property; Proteins; RNA Folding; Resolution; Running; Sampling; Signal Pathway; Signaling Protein; Simulate; Site; Solvents; Source Code; Speed; System; Techniques; Temperature; Testing; Thermodynamics; Time; Variant; Water; aqueous; base; design; evaluation/testing; improved; kinematics; molecular dynamics; programs; protein protein interaction; protein structure; protein structure prediction; public health relevance; research study; restraint; screening; simulation; tool; virtual

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. !

描述（由申请人提供）：该提案响应 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。 Amber 是一款流行的软件包，已授权给 800 多家学术和行业机构，用于模拟分子系统的结构、热力学和动力学特性。流行的 Amber ff99SB 力场有 885 次引用，该力场由 PI Carlos Simmerling 在石溪开发。 Simmerling小组是负责Amber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成为实验研究的重要对应物，以了解生物分子的机制并发现抑制生物分子的药物。流行的虚拟筛选程序 DOCK 直接与 Amber 连接。这里提出的软件改进的目标之一是减少开发新药所需的时间。我们在此提出 Amber 的新发展，以满足该领域最紧迫的需求。目标 1，溶剂化：我们将采用改进的溶剂化模型：(a) SEA 半显式水模型和 (b) 新的广义 Born 模型。目标 2，采样：我们将添加快速且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，该方法对稀疏和噪声数据的构象进行采样； (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) 限制和转移方法，该方法计算生物分子的两种不同构象之间的自由能差异。我们将把我们最近开发的算法合并到 Amber 生产代码中进行分发，并使用 CUDA 将代码移植到最近开发的 Amber 的 GPU 版本。 ！