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.

项目总结