Addressing biomedical challenges with computational mechanics and big data

项目摘要 该项目的目标是开发更好的分子算法， 机械和灵活的对接，纳入新的数据，并使用的方法， 扩展了生物大分子的三维原子模型， 它们的配体复合物与预测的部分和同源性模型。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 超过60个研究实验室，并使用结构模型来了解 生物学功能和治疗作用。我们将密切合作， 与斯卡格斯药学院的几个实验室合作 科学，UCSD，UCSD医学院，生物信息学和系统生物学 在UCSD和几个美国机构的计划。SSPPS的合作者包括 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， hookworms）、Jair L. Siqueira-Neto（HTS核心，锥虫病，利什曼病， Anjan Debnath（阿米巴病）、Carlo Ballatore和Dionicio Siegel （药物化学）。Nuno Bandeira和Pieter Dorrestein（NIH/NCRR中心 计算质谱），将有助于合并或生成 质谱数据。我们还将研究新的治疗方法， 疾病，分子作用机制，以及与新疾病相关的探针 途径与实验室从加州大学圣地亚哥分校健康科学部门（西尔维奥 Gutkind，Joseph Califano，Don Durden，Nunzio Bottini，Olivier Harismendy - 癌基因组学，Pavel Pevzner，Lev Tsimring）和几个美国实验室（Mark 耶格尔，UVa，伊琳娜Artsimovich，OHSU，安德烈奥斯特曼，SBP- 医学研究所，EricDebler，Jefferson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- 耐药突变和了解多靶点药物药理学。我们 将项目期间产生的所有数据和程序公开 available.

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.