Sixth International Workshop on X-ray Damage to Biological Crystalline Samples

描述(由申请者提供)：请为2010年3月11日至13日在斯坦福同步辐射光源(SSRL)举行的第六届生物晶体样品X射线损伤国际研讨会提供部分支持。X射线晶体衍射是迄今获得蛋白质、核酸及其络合物的详细原子分辨三维结构的最佳工具；了解结构对于了解它们的相互作用机制和模式至关重要，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。现代同步加速器源的发展提供了非常强的X射线束，对这种方法可以处理的靶的数量产生了巨大的影响，包括医学上重要的分子和已建立的或潜在的药物靶。然而，在实验过程中持续暴露在如此强烈的X射线下会对晶体样品造成重大损害，要么阻止成功的结构解决方案，要么危及从结构中提取的生物信息。生物晶体样品X射线损伤问题国际讲习班是介绍电离辐射对生物晶体材料影响的最新实验和进展的主要论坛。讲习班的目的是促进对大分子晶体中辐射损伤过程的详细了解，并鼓励开发新的技术，以减轻或纠正损伤对衍射数据和由此产生的结构模型的影响。其中一些演讲以同行评议文章的形式发表在《同步辐射杂志》的特刊上。这一做法确保了更广泛的传播，并为智能使用同步辐射X射线光束线进行结构生物学研究提供了坚实的基础。该系列第六期研讨会的计划将由一个由该研究领域的领导者组成的科学委员会来组织。会议主题将包括：减少和减轻辐射损伤；生物分子的辐射化学和辐射分解；生物结晶学中对辐射损伤认识的进展；对辐射损伤的影响进行校正；金属蛋白的减少；利用辐射损伤来研究晶体蛋白质的大分子功能；电子显微镜和电子结晶学中的辐射损伤；研究辐射损伤的非结晶学方法；以及目前正在上线的强短脉冲X射线源的使用。 与公共卫生相关(由申请人提供)：蛋白质在生物学中扮演着至关重要的角色，因为它们负责生命机械：例如，食物的消化、大脑中的信号传递、肌肉的运动等。通过用X射线结晶学找出它们的三维形状，我们能够获得关于它们作用机制的宝贵信息，并且我们还能够了解它们如何以及为什么会发生故障(例如通过将细胞从正常状态转变为癌症状态)，这些知识为针对疾病的药物设计提供了信息，并最终能够导致更好的治疗方法来改善人类健康。然而，X射线破坏了感兴趣的分子内部和之间的原子键，这可能导致实验失败或产生误导结构。第六届生物晶体样品X射线损伤问题国际讲习班旨在增进对X射线对生物大分子影响的了解，并将这一知识应用于开发减轻或纠正这些影响的技术。

DESCRIPTION (provided by applicant): Partial support is requested for The Sixth International Workshop on X-ray Damage to Biological Crystalline Samples to be held at the Stanford Synchrotron Radiation Light Source (SSRL) from March 11th -13th 2010. X-ray crystal diffraction is the best tool available to date to obtain a detailed atomic resolution three-dimensional structure of protein, nucleic acids and their complexes; knowledge of the structure 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. The development of modern synchrotron sources, which provide very intense X-ray beams, has had a dramatic impact on the number of target that can be tackled by this method, including medically important molecules and established or potential drug targets. However, continuous exposure to such intense X-rays during the experiment can cause significant damage to the crystalline sample, either preventing successful structural solution or compromising the biological information extracted from the structure. The International Workshops on X-ray Damage to Biological Crystalline Samples are the main forum for the presentation of the latest experiments and advances in understanding the effects of ionizing radiation on crystalline biological materials. The objectives of the Workshops are to further the detailed knowledge of radiation damage processes in macromolecular crystals, and to encourage the development of new techniques to mitigate or correct for the effects of damage on diffraction data and the resulting structural model. Some of the presentations are published as peer-reviewed articles in special issues of the Journal of Synchrotron Radiation. This practice ensures wider dissemination and provides a strong basis for intelligent use of synchrotron X-ray beamlines for structural biology studies. The program for Sixth Workshop in the series will be organized by a scientific committee composed of leaders in this research field. Session topics will include reduction and mitigation of radiation damage, radiation chemistry and radiolysis of biological molecules, progress in the understanding of radiation damage in biological crystallography, correcting for the effects of radiation damage, reduction of metalloproteins, the use of radiation damage to study macromolecular function of crystalline proteins, radiation damage in electron microscopy and electron crystallography, non-crystallographic methods to study radiation damage and the use of intense short pulsed X-ray sources, which are currently coming on line. PUBLIC HEALTH RELEVANCE (provided by the applicant): Proteins play a vital role in biology in that they are responsible for the machinery of life: e.g. digestion of food, signaling in the brain, movement of muscles etc. By finding their three-dimensional shape by X-ray crystallography, we are able to gain valuable information on their mechanism of action, and also to understand how and why they malfunction (e.g. by switching a cell from its normal state into a cancerous state), knowledge that informs drug design against disease and can lead eventually to better treatments to improve human health. However, the X-rays disrupt atomic bonds within and between the molecules of interest, which can result in failed experiments or in misleading structures. The Sixth International Workshop on X-ray Damage to Biological Crystalline Samples seeks to advance the understanding of the effects of X-rays on biological macromolecules and to apply this knowledge to the development of techniques to mitigate or correct these effects.