Diffraction Methods in Molecular Biology Gordon Research Conference

描述（由申请人提供）：戈登研究会议（GRC）将于2010年7月18日至7月23日在缅因州刘易斯顿贝茨学院举行，主题为“结构生物学中的衍射方法”。了解生物分子的三维结构对于理解它们的机制和相互作用模式至关重要，并为以有益于人类健康的方式调节它们的活动提供了机会。迄今为止，x射线晶体学是测定生物分子（蛋白质和核酸及其复合物）高分辨率结构的最强大的技术。方法上的进步大大扩大了现在可以成功解决的目标范围。最近的研究重点包括高度复杂的蛋白质- RNA组合，如70S细菌核糖体，非常大的含脂病毒，以及参与转录的复合物。测定的固有膜蛋白结构的数量也有了非常显著的增加。其中包括介导对抗癌药物（P糖蛋白）耐药性的ABC转运蛋白，以及最近一些G蛋白偶联受体的结构。gpcr与许多疾病有关，是近50%的现代药物的靶标。在更实际的层面上，同步加速器束流线的进步促进了数百个数据集的快速收集，这些数据集是许多领先制药公司采用的“片段拟合”方法进行药物筛选所需的。为了解决越来越具有挑战性的生物系统，方法论的持续发展是必不可少的。这个GRC是美国的主要论坛，用于介绍和讨论衍射方法各个方面的最新进展，从结晶到模型构建和改进。2010年的会议将由Andrew Leslie （MRC LMB，剑桥）主持，Ana Gonzalez（斯坦福同步辐射实验室）担任副主席，并将包括该领域许多关键软件和硬件开发人员的演讲。会议主题将包括结晶和数据收集，辐射损伤，同步加速器的发展，互补技术（SAXS，电子断层扫描和光谱学），结构解决和改进，具有挑战性的问题（包括膜蛋白），选定海报的口头展示，模型构建和未来的成像方法，如自由电子激光和衍射成像。

DESCRIPTION (provided by applicant): Partial support is requested for the Gordon Research Conference (GRC) on "Diffraction Methods in Structural Biology" to be held at Bates College, Lewiston, Maine from 7/18/2010 - 7/23/2010. Knowledge of the three dimensional structures of biological molecules is essential in order to understand their mechanism and modes of interaction, and provides an opportunity to modulate their activity in a way that is beneficial to human health. X-ray crystallography is by far the most powerful technique for the high-resolution structure determination of biological molecules (proteins and nucleic acids and their complexes). Advances in methodology have dramatically extended the range of targets that can now be tackled successfully. Recent highlights include highly complex protein- RNA assemblies such as the 70S bacterial ribosome, very large lipid containing viruses, and complexes involved in transcription. There has also been a very significant increase in the number of intrinsic membrane protein structures determined. These include ABC transporters that mediate resistance to anticancer drugs (P glycoprotein) and most recently the structures of a number of G Protein Coupled Receptors. GPCRs and are involved in many diseases and are the targets of almost 50% of modern medicinal drugs. On a more practical level, advances at synchrotron beam lines have facilitated the rapid collection of the hundreds of datasets required for the "fragment fitting" approach to drug screening adopted by many leading pharmaceutical companies. The continued development of methodology is essential in order to tackle ever more challenging biological systems. This GRC is the main forum in the United States for the presentation and discussion of recent advances in all aspects of diffraction methods, ranging from crystallization to model building and refinement. The 2010 meeting will be chaired by Andrew Leslie (MRC LMB, Cambridge) with Ana Gonzalez (Stanford Synchrotron Radiation Laboratory) as vice chair, and will include presentations from many of the key software and hardware developers in the field. Session topics will include crystallization and data collection, radiation damage, synchrotron developments, complementary techniques (SAXS, electron tomography and spectroscopy), structure solution and refinement, challenging problems (including membrane proteins), oral presentation of selected posters, model building and imaging methods of the future such as free electron lasers and diffractive imaging. PUBLIC HEALTH RELEVANCE: Drugs achieve their therapeutic effects by binding tightly and specifically to a target protein, by virtue of shape complementarily, in a way that interferes with the normal functioning of that protein. The three dimensional shape of proteins can be determined by X-ray diffraction methods from crystals of the protein, providing a route to the rational design of drugs. The 2010 Gordon Research Conference in Diffraction Methods in Structural Biology seeks to advance the techniques used in structure determination by providing a forum for the presentation and discussion of recent developments.