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

基本信息

批准号：
9974519
负责人：
CARLOS SIMMERLING
金额：
$ 30.42万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9974519
关键词：
Address Adopted Algorithms Amber Biological Biomedical Computing Code Communities Companions Complex Computer Models Computer Simulation Computer software Consumption DNA Data Development Documentation Evaluation Funding Gene Expression Goals Grain Health Hybrids Industry Informatics Institution Journals Kinetics Lead Maintenance Methodology Methods Modeling Molecular Molecular Computations Molecular Conformation Neck Nucleic Acids Pharmaceutical Preparations Pharmacotherapy Production Productivity Property Protein Engineering Proteins Publishing RNA Folding Resolution Running Sampling Schedule Signal Pathway Signaling Protein Site Small RNA Solvents Source Code Speed Structure System Technology Temperature Testing Thermodynamics Time Variant Water Work aqueous base big-data science design drug discovery experimental study improved kinematics large datasets molecular dynamics nanomaterials programs protein protein interaction screening program simulation tool tutoring virtual screening

项目摘要

Project Summary This proposal responds to PA-14-156, Extended Development, Hardening and Dissemination of Technologies in Biomedical Computing, Informatics and Big Data Science. The goal of this program is to support the continued development, maintenance, testing and evaluation of existing software, matching our proposal. Amber is a very popular software package, used by academic and industry institutions, for simulating the structural, thermodynamic and kinetic properties of molecular systems. The free version of Amber has been downloaded by over 10,000 unique users. There are 3,500 citations to the widely adopted Amber ff99SB protein force field, developed at Stony Brook by PI Carlos Simmerling. The Simmerling group is one of the six academic labs responsible for leading the Amber software maintenance and development effort. 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, providing improvements to this widely used program for drug discovery. Other widely used programs also interface with Amber. Productivity in our prior funding period was excellent, leading to articles published in PNAS (2), JACS (3), JCTC (4) and other high-impact journals, with others currently in review. Several new versions of Amber were released. We propose here new developments for Amber, addressing two of 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 fast but reasonably accurate Generalized Born implicit water 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 very fast Kinetic-Loop-Closure and Constrained-Loop-Closure methods for sampling loop conformations. Following our practice over the past 20 years, we will openly share our results, parameters and methods, and incorporate them into the Amber production code for distribution with fully documented source code, along with full documentation, test cases, and tutorials. New versions follow an annual release schedule.

项目摘要该提案对PA-14-156的响应，扩展的发展，硬化和传播生物医学计算，信息学和大数据科学的技术。目标的目标计划是为了支持持续的开发，维护，测试和评估现有软件，与我们的建议相匹配。 Amber是学术和行业机构使用的非常受欢迎的软件包，用于模拟分子系统的结构，热力学和动力学特性。琥珀的免费版本已由10,000多名唯一用户下载。被广泛采用的引用有3500个琥珀FF99SB蛋白力场，由Pi Carlos煮至Stony Brook。慢跑小组是负责领导琥珀软件维护和的六个学术实验室之一发展工作。使用琥珀和其他软件包的计算分子动力学模拟具有成为实验研究的重要对应者，以了解生物分子，并发现药物抑制它们。流行的虚拟筛选程序称为直接与琥珀色的码头接口，为这种广泛使用的药物提供了改进发现。其他广泛使用的程序也与Amber接口。在我们以前的资金期间的生产力非常好，导致PNA中发表的文章（2）， JACS（3），JCTC（4）和其他高影响力期刊，目前正在审查中。几个新琥珀版本已发布。我们在这里为琥珀提供新的发展，以满足领域。 AIM 1，溶剂化：我们将合并改进的溶剂化模型：（a）海洋半明确的水模型和（b）快速但相当准确的广义上的隐式水模型。 AIM 2，采样：我们将添加快速和针对性的采样方法：（a）通用工具哈密顿交换和热复制交换分子动力学，（b）非常快速的动力学环闭合和采样环路的约束环闭合方法构象。在过去20年中的实践之后，我们将公开分享我们的结果，参数和方法，并将它们纳入琥珀生产代码中，以便完全分发记录了源代码，以及完整的文档，测试用例和教程。新版本遵循年度发布时间表。