Computer Cluster for Computational Biology and Biophysics

计算生物学和生物物理学计算机集群

• 批准号: 8826397
• 负责人: Ronald Levy
• 金额: $ 44.23万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-19 至 2016-05-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8826397
• 关键词: AIDS/HIV problem; Algorithms; Anesthetics; Antibodies; Binding; Binding Proteins; Biochemistry; Biophysics; Computational Biology; Coupled; Data Set; Disease; Drug Design; Equilibrium; Equipment; Funding; Gated Ion Channel; Genomics; Grant; Human; Human Resources; Ion Channel; Linux; Markov chain Monte Carlo methodology; Membrane; Methods; Modeling; Nature; Performance; Population; Population Genetics; Postdoctoral Fellow; Process; Proteins; Public Health; Regulation; Research; Sampling; Staging; Statistical Methods; Structure; Students; TNFRSF5 gene; United States National Institutes of Health; Universities; base; computer cluster; design; improved; metalloenzyme; model design; molecular dynamics; programs; protein folding; protein structure; shared memory; simulation; structural biology; voltage

 DESCRIPTION: This is a proposal to purchase a Computer Cluster to support six NIH-funded research groups at Temple University (in total, more than 50 students, post-docs, and senior personnel) carrying out diverse projects spanning biophysics, biochemistry, structural biology, population genetics and genomics. Specifically, it is proposed to acquire a Linux cluster containing 40 compute nodes with four 16-core processors each, for 2560 processor cores in total. The cluster will provide the capacity that is optimized for the computing needs of the NIH supported projects described in this proposal. The projects for which the requested equipment will be used include: Protein-Ligand Binding and Allostery: Effective Potentials, Advanced Sampling Methods, and Applications (R.M. Levy); Permeation of Biologically Active Molecules and Regulation of Membrane Channels by Molecular Dynamics Simulations (M.L. Klein, V. Carnevale, and G. Fiorin); Optimization of New Statistical Scoring Terms in the Rosetta Program and Application to Antibody- Specific Computational Design (R. Dunbrack); Early Stages of Protein Folding Explored by Experimental and Computational Approaches (H. Roder and V. Voelz); Designing and Modeling Spiroligomer Based Metalloenzyme Mimics (C. Schafmeister), and Implementation of Statistical Methods for Human Population Genomics (E.J. Hey). These computationally intensive projects are currently supported by seven R01 grants, one P01 grant and one P50 grant. The requested hardware consists of a balanced combination of compute nodes with high- throughput low-latency InfiniBand interconnect and a high-performance storage appliance to accommodate projects which require shared memory in-node parallelization and loosely coupled message passing parallel or uncoupled independent processes operating on independent data sets. A key aspect of the proposed computer cluster acquisition is to obtain greater MPI parallel capabilities needed for modern atomic simulations of proteins using advanced sampling algorithms, molecular dynamics simulations of membranes and ion channels, and Markov Chain Monte-Carlo simulations employed in population genetics and genomics modeling. The public health-related relevance of the projects described in this proposal include improving methods for the characterization of protein structures (and assemblies) as a basis for structure based drug design for treatments of HIV/AIDS and other diseases, as well as understanding the nature of the binding of anesthetics to voltage-gated ion channels.

 描述：这是一项购买计算机集群的提案，以支持天普大学 6 个 NIH 资助的研究小组（总共 50 多名学生、博士后和高级人员）开展涵盖生物物理学、生物化学、结构生物学、群体遗传学和基因组学的各种项目。具体来说，建议购买一个包含 40 个计算节点的 Linux 集群，每个计算节点有 4 个 16 核处理器，总共 2560 个处理器核心。该集群将提供针对本提案中描述的 NIH 支持项目的计算需求进行优化的容量。将使用所需设备的项目包括：蛋白质-配体结合和变构：有效潜力、高级采样方法和应用（R.M. Levy）；通过分子动力学模拟实现生物活性分子的渗透和膜通道的调节（M.L. Klein、V. Carnevale 和 G. Fiorin）； Rosetta 程序中新统计评分项的优化及其在抗体特异性计算设计中的应用 (R. Dunbrack)；通过实验和计算方法探索蛋白质折叠的早期阶段（H. Roder 和 V. Voelz）；基于螺低聚物的金属酶模拟物的设计和建模（C. Schafmeister），以及人类群体基因组学统计方法的实施（E.J. Hey）。这些计算密集型项目目前由 7 项 R01 拨款、1 项 P01 拨款和 1 项 P50 拨款支持。所需的硬件由具有高吞吐量、低延迟 InfiniBand 互连的计算节点和高性能存储设备的平衡组合组成，以适应需要共享内存节点内并行化和松散耦合消息传递并行或在独立数据集上运行的非耦合独立进程的项目。所提出的计算机集群采集的一个关键方面是使用先进的采样算法、膜和离子通道的分子动力学模拟以及群体遗传学和基因组学建模中使用的马尔可夫链蒙特卡罗模拟来获得现代蛋白质原子模拟所需的更大的 MPI 并行能力。该提案中描述的项目与公共卫生相关的相关性包括改进蛋白质结构（和组装）的表征方法，作为治疗艾滋病毒/艾滋病和其他疾病的基于结构的药物设计的基础，以及了解麻醉剂与电压门控离子通道结合的性质。

项目成果

Absolute Protein Binding Free Energy Simulations for Ligands with Multiple Poses, a Thermodynamic Path That Avoids Exhaustive Enumeration of the Poses

• DOI: 10.1002/jcc.26078
• 发表时间: 2019-10
• 期刊: Journal of Computational Chemistry
• 影响因子: 3
• 作者: Y. Sakae;Bin W. Zhang;R. Levy;N. Deng

Potts Hamiltonian Models and Molecular Dynamics Free Energy Simulations for Predicting the Impact of Mutations on Protein Kinase Stability.

用于预测突变对蛋白激酶稳定性影响的波茨哈密顿模型和分子动力学自由能模拟。

• DOI: 10.1021/acs.jpcb.3c08097
• 发表时间: 2024
• 期刊: The journal of physical chemistry. B
• 作者: Thakur,Abhishek;Gizzio,Joan;Levy,RonaldM
• 通讯作者: Levy,RonaldM

Ligand Binding Thermodynamic Cycles: Hysteresis, the Locally Weighted Histogram Analysis Method, and the Overlapping States Matrix

• DOI: 10.1021/acs.jctc.9b00740
• 发表时间: 2020-01-01
• 期刊: JOURNAL OF CHEMICAL THEORY AND COMPUTATION
• 影响因子: 5.5
• 作者: Cui, Di;Zhang, Bin W.;Levy, Ronald M.
• 通讯作者: Levy, Ronald M.

Global and local mechanical properties control endonuclease reactivity of a DNA origami nanostructure.

全局和局部机械特性控制 DNA 折纸纳米结构的核酸内切酶反应性。

• DOI: 10.1093/nar/gkaa080
• 发表时间: 2020
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Suma,Antonio;Stopar,Alex;Nicholson,AllenW;Castronovo,Matteo;Carnevale,Vincenzo
• 通讯作者: Carnevale,Vincenzo