Diffraction Methods in Molecular Biology Gordon Research Conference

分子生物学中的衍射方法戈登研究会议

基本信息

批准号：
7902980
负责人：
Nancy Ryan Gray
金额：
$ 0.5万
依托单位：
GORDON RESEARCH CONFERENCES
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-01 至 2011-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7902980
关键词：
ATP-Binding Cassette Transporters Adopted Antineoplastic Agents Binding Biological Collection Complex Computer software Crystallization Data Collection Data Set Development Disease Drug Design Electrons Future G-Protein-Coupled Receptors Genetic Transcription Health Human Image Integral Membrane Protein Knowledge Laboratories Lasers Lipids Maine Mediating Membrane Proteins Methodology Methods Modeling Molecular Biology Nucleic Acids Oral P-Glycoprotein P-Glycoproteins Pharmaceutical Preparations Pharmacologic Substance Preclinical Drug Evaluation Proteins RNA Radiation Research Resistance Resolution Ribosomes Route Shapes Solutions Spectrum Analysis Structure Synchrotrons Techniques Therapeutic Effect United States Virus X ray diffraction analysis X-Ray Crystallography X-Ray Diffraction biological systems college electron tomography imaging modality meetings posters protein complex protein function protein structure public health relevance structural biology symposium synchrotron radiation three dimensional structure

项目摘要

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.

说明（由申请人提供）：请求部分支持将于 7/18/2010 至 7/23/2010 在缅因州刘易斯顿贝茨学院举行的关于“结构生物学中的衍射方法”的戈登研究会议 (GRC)。了解生物分子的三维结构对于理解其相互作用的机制和模式至关重要，并提供了以有益于人类健康的方式调节其活动的机会。 X 射线晶体学是迄今为止用于生物分子（蛋白质、核酸及其复合物）高分辨率结构测定的最强大技术。方法论的进步极大地扩展了现在可以成功实现的目标范围。最近的亮点包括高度复杂的蛋白质-RNA 组装体，例如 70S 细菌核糖体、非常大的含脂质病毒以及参与转录的复合物。确定的内在膜蛋白结构的数量也有了非常显着的增加。其中包括介导抗癌药物（P 糖蛋白）耐药性的 ABC 转运蛋白以及最近的一些 G 蛋白偶联受体的结构。 GPCR 与多种疾病有关，是近 50% 现代药物的靶标。在更实际的层面上，同步加速器光束线的进步促进了许多领先制药公司采用的药物筛选“片段拟合”方法所需的数百个数据集的快速收集。为了应对更具挑战性的生物系统，方法论的持续发展至关重要。该 GRC 是美国的主要论坛，用于展示和讨论衍射方法各个方面（从结晶到模型构建和细化）的最新进展。 2010 年会议将由 Andrew Leslie（剑桥 MRC LMB）主持，Ana Gonzalez（斯坦福同步辐射实验室）担任副主席，会议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、同步加速器发展、补充技术（SAXS、电子断层扫描和光谱学）、结构解决和细化、挑战性问题（包括膜蛋白）、选定海报的口头展示、模型构建和成像方法未来的技术，例如自由电子激光器和衍射成像。公共健康相关性：药物通过与目标蛋白紧密、特异地结合，凭借形状互补，以干扰该蛋白正常功能的方式实现其治疗效果。通过X射线衍射方法可以从蛋白质晶体中确定蛋白质的三维形状，为药物的合理设计提供了途径。 2010 年结构生物学衍射方法戈登研究会议旨在通过提供一个展示和讨论最新进展的论坛来推进结构测定中使用的技术。