Addressing biomedical challenges with computational mechanics and big data

项目总结 这个项目的目标是开发更好的分子算法。 机械和灵活的对接，整合新数据，并使用这些方法 扩展生物大分子的三维原子模型集和 它们的配体络合物与预测的部分和同源模型。这些 模型将被用来识别新的候选治疗方案并预测 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几个实验室 UCSD、UCSD医学院、生物信息学和系统生物学 加州大学圣迭戈分校和几个美国机构的项目。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(结晶学，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)，安詹·德布纳特(阿米巴病)，卡洛·巴拉托雷和迪奥尼西奥·西格尔 (药物化学)。Nuno Bandeira和Pieter Dorrestein(NIH/NCRR中心 对于计算质谱学)，将有助于合并或生成 质谱学数据。我们还将致力于几种新的治疗方法 疾病、分子作用机制和与新疾病相关的探索 与UCSD健康科学部门(Silvio)实验室的合作途径 古特金德，约瑟夫·卡里法诺，唐·德登，农齐奥·博蒂尼，奥利维尔·哈里斯门迪- 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·阿茨莫维奇，OHSU，安德烈·奥斯特曼，SBP- 医学研究所，Eric Debler，杰斐逊大学)。更好的方法，更好的模型， 更好的数据将有助于对疾病相关途径、药物的新探测器 重新调整用途和设计新的药物组合，了解药物- 耐药突变，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之于众 可用。

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.