Addressing biomedical challenges with computational mechanics and big data

利用计算力学和大数据解决生物医学挑战

• 批准号: 10402329
• 负责人: RUBEN ABAGYAN
• 金额: $ 38.43万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10402329
• 关键词: 3-Dimensional; Address; Algorithms; Amebiasis; Antiviral Agents; Area; Big Data; Bioinformatics; Biological; Biological Process; Biological Response Modifier Therapy; Cells; Collaborations; Complex; Crystallography; Data; Disease; Disease model; Docking; Drug Design; Drug Targeting; Drug resistance; Head; Health Sciences; Homology Modeling; Hookworms; Human; Institutes; Institution; Laboratories; Laboratory Research; Leishmaniasis; Ligands; Mass Spectrum Analysis; Mechanics; Methods; Modeling; Molecular Mechanisms of Action; Molecular Structure; National Center for Research Resources; Pathway interactions; Pharmaceutical Chemistry; Pharmacologic Substance; Pharmacology; Pharmacy Schools; Publishing; Schistosomiasis; Science; Structural Models; Systems Biology; Therapeutic; Trypanosomiasis; United States National Institutes of Health; Work; cancer genomics; chemokine receptor; drug action; drug repurposing; flexibility; human disease; macromolecule; medical schools; molecular mechanics; novel drug combination; novel therapeutics; programs; resistance mutation; screening; therapeutic candidate

PROJECT SUMMARY The objective of this project is to develop better algorithms for molecular mechanics and flexible docking, incorporate new data, and use the methods to expand the set of three-dimensional atomic models of bio-macromolecules and their ligand complexes with predicted parts and homology models. These models will be used to identify new therapeutic candidates and predict mechanism of action of drugs. Since 2007 we collaborated and published with over sixty research laboratories and used structural models to understand biological function and therapeutic action. We will work in close collaboration with several laboratories at Skaggs School of Pharmacy and Pharmaceutical Sciences, UCSD, UCSD Medical School, Bioinformatics and Systems Biology Program at UCSD and several US Institutions. The SSPPS collaborators include Tracy Handel (chemokine receptors), James McKerrow (head of CDIPD center), Larissa Podust (crystallography, CDIPD), Conor Caffrey (schistosomiasis, hookworms), Jair L. Siqueira-Neto (HTS core, trypanosomiasis, leishmaniasis, antivirals), Anjan Debnath (amebiasis), Carlo Ballatore and Dionicio Siegel (medicinal chemistry) . Nuno Bandeira and Pieter Dorrestein (NIH/NCRR Center for Computational Mass Spectrometry), will help with incorporating or generating mass spectrometry data. We will also work on new treatments for several diseases, molecular mechanisms of action, and probes for new disease related pathways with the laboratories from UCSD Health Sciences Departments (Silvio Gutkind, Joseph Califano, Don Durden, Nunzio Bottini, Olivier Harismendy - oncogenomics, Pavel Pevzner, Lev Tsimring) and several US laboratories (Mark Yeager, UVa, Irina Artsimovich, OHSU, Andrei Osterman, SBP- Med.Res.Institute, Eric Debler, Jefferson Uni.). Better methods, better models, better data will help with new probes for disease-related pathways, drug repurposing and designing new drug combinations, understanding drug- resistance mutations, and understanding multi-target drug pharmacology. We will make all the data and programs produced during the project publicly available.

项目概要 该项目的目标是开发更好的分子算法 力学与灵活对接，融入新数据，利用方法 扩展生物大分子的三维原子模型集 它们的配体复合物与预测的部分和同源模型。这些 模型将用于识别新的治疗候选者并预测 药物的作用机制。自 2007 年以来，我们与以下机构合作并出版了 超过六十个研究实验室并使用结构模型来理解 生物学功能和治疗作用。我们将密切合作 与斯卡格斯药学和制药学院的多个实验室 科学，加州大学圣地亚哥分校，加州大学圣地亚哥分校医学院，生物信息学和系统生物学 加州大学圣地亚哥分校和几家美国机构的项目。 SSPPS 合作者包括 Tracy Handel（趋化因子受体）、James McKerrow（CDIPD 中心负责人）、 Larissa Podust（晶体学、CDIPD）、Conor Caffrey（血吸虫病、 钩虫）、Jair L. Siqueira-Neto（HTS 核心、锥虫病、利什曼病、 抗病毒药物）、Anjan Debnath（阿米巴病）、Carlo Ballatore 和 Dionicio Siegel （药物化学）。 Nuno Bandeira 和 Pieter Dorrestein（NIH/NCRR 中心 用于计算质谱法），将有助于合并或生成 质谱数据。我们还将致力于针对多种疾病的新疗法 疾病、作用分子机制以及新疾病相关的探针 与加州大学圣地亚哥分校健康科学系 (Silvio Gutkind、Joseph Califano、Don Durden、Nunzio Bottini、Olivier Harismendy - 肿瘤基因组学，Pavel Pevzner，Lev Tsimring）和几个美国实验室（Mark 耶格尔，UVa，伊琳娜·阿尔西莫维奇，OHSU，安德烈·奥斯特曼，SBP- 医学研究研究所，埃里克·德布勒，杰斐逊大学）。更好的方法、更好的模型、 更好的数据将有助于疾病相关途径、药物的新探针 重新利用和设计新的药物组合，了解药物 耐药突变，并了解多靶点药物药理学。我们 将公开项目期间产生的所有数据和程序 可用的。