SEARCH FOR AVIAN FLU INHIBITORS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 随着禽流感大流行的威胁迫在眉睫，现有的抗病毒抑制剂的效果可能有限 由于流感病毒的高变异率。虽然有大量的投资在制药和 生物技术产业要开发新疫苗和新干预手段，需要更多的基础研究 了解禽流感感染生命周期的作用机制，特别是在宿主选择性和关键方面 病毒复制途径中的酶。H5N1 HA蛋白和NA酶的最新结晶提供了新的 药物发现和转化医学研究的机会。 该项目在NBCR的研究和开发中发挥着综合作用，并为与 世界各地的研究人员。我们将开发全面的解决方案来使用松弛复数方法和分子 药物开发中的动力学，从蛋白质结构的制备，到MD快照的选择，再到模拟 使用分子建模技术的突变。MD技术也将被开发来执行对接的重新评分 利用AutoDock和Hierarchy从虚拟筛选实验中精选热门歌曲的实验 筛查程序。这些研究的大量计算要求使用超级计算机，例如 Bluegene，以及开放科学网格、TeraGrid等分布式资源和社区资源，如 世界社区电网。由此产生的软件通过对这些新算法的封装将会有更大的 在多种疾病和蛋白质配体相互作用机制研究中的应用

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. As the Avian flu pandemic threat is looming in the horizon, existing antiviral inhibitors are likely to be of limited efficacy due to the high mutation rate of the flu virus. While there is significant investment in the pharmaceutical and biotechnology industry to develop new vaccines and new means of intervention, more fundamental research is required to understand the mechanism of action of Avian flu infectious life cycle, especially in terms of host selectivity and key enzymes in the viral replication pathway. The recent crystallization of the H5N1 HA protein and NA enzyme offer new chances for drug discovery and translational medicine research. This project plays an integrative role in NBCR research and development, as well as opportunities for collaboration with researchers worldwide. We'll develop comprehensive solutions to the use of Relaxed Complex method and Molecular Dynamics in drug development, from preparation of protein structures, to selection of MD snapshots, to simulations of mutations using molecular modeling techniques. The MD techniques will also be developed to perform rescoring of docking experiments to refine the selection of top hits from virtual screening experiments using AutoDock and hierarchical screening procedures. The large computational requirements for these studies demand the use of supercomputers such as the BlueGene, as well as distributed resources such as the Open Science Grid, TeraGrid and community resources such as the World Community Grid. The resulting software through the encapsulation of these new algorithms will be of greater use to a wide range of diseases and mechanistic studies of protein ligand interactions