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：这是一项提议，购买计算机群，以支持Temple University的六个由NIH资助的研究小组（总共有50多名学生，后DOC​​和高级人员），他们进行了跨越生物物理学，生物化学，结构生物学，人群遗传学和基因组学的潜水项目。具体而言，提议获得一个包含40个具有4个16核处理器的计算节点的Linux群集，总共2560个处理器核心。该集群将为本提案中描述的NIH支持的项目的计算需求提供优化的能力。使用所请求的设备的项目包括：蛋白质配体结合和变构：有效潜力，高级抽样方法和应用程序（R.M. Levy）；通过分子动力学模拟（M.L。Klein，V。Carnevale和G. Fiorin）对生物活性分子的渗透和膜通道的调节；在Rosetta计划中优化新的统计评分术语，并应用于抗体特定的计算设计（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）；设计和建模基于螺旋藻的金属酶模拟物（C. schafmeister），并实施人群基因组学统计方法（E.J. Hey）。这些计算密集型项目目前得到了七项R01补助金，一项P01赠款和一项P50赠款的支持。请求的硬件由具有高通量低延迟的Infiniband Internect和高性能存储设备的计算节点的平衡组合组成，以适应需要共享内存内存并行的项目，并松散耦合的消息传递传递并行或UNC的独立流程在独立的数据集上运行。提议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Markov Chain Chain Chain Monte-Carlo模拟进行了种群遗传学和种植体模型。本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（和组件）的表征方法，作为基于结构的艾滋病毒/艾滋病治疗方法的基础药物设计的基础，以及了解麻醉剂对电压门控离子通道的结合的性质。

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