Instrument Development to Reduce Radiation Damage in Macromolecular Crystallography

该奖项旨在开发仪器以减少大分子晶体学中辐射损伤的有害影响，这是该领域的主要限制之一。仪器将被添加到同步辐射光束线。估计晶体存活率的潜在改善对于较大晶体为60%，对于小片状晶体为10倍。该策略的基本思想是尽可能地将衍射发生的区域与损伤发生的区域分离。这种可能性是存在的，因为损坏的主要原因是通过光电效应吸收x射线而产生的高能光电子（PE）。在主要包含低Z原子的生物晶体中，PE的能量将比X射线的能量小约500 eV，因此通常高达20 keV。对于这样的高能PE的初始停止功率，即，每单位距离的能量损失，是相当小的，并大大增加，因为他们慢下来。20 keV PE行进的距离为6微米。因此，通过将X射线集中在间隔略大于6微米的小区域中，可以实现分离衍射区域和受损区域的目标。 在控制或减少初级辐射损伤方面的任何改进将对所有大分子X射线晶体学产生重大影响，例如，为非常大的结构开辟新的晶体学，提高标准尺寸晶体的结构分辨率，并从非常小的片状晶体中获得有用的结构信息。通过减少X射线晶体学过程中对晶体的损伤，这种仪器将加速晶体结构的积累和对生物大分子结构-功能关系的理解。该项目是跨学科的，涉及物理学家和一名生物学家，也是国际性的，涉及一名以色列物理学家。

This award is for developing instrumentation to reduce the deleterious effects of radiation damage in macromolecular crystallography, which is one of the major limitations in the this field. The instrumentation will be added to synchrotron radiation beamlines. Estimates of potential improvements in crystal survival are 60% for larger crystals and up to a factor of 10 for small platelet-shaped crystals. The basic idea of the strategies is to separate as much as possible the region where diffraction occurs from the region where the damage occurs. This possibility exists, because the primary cause of damage is the energetic photoelectrons (PE's) created by the absorption of x-rays through the photoelectric effect. In bio-crystals that predominantly contain low Z atoms the PE's will have energies about 500 eV less than those of the x-rays, thus typically up to 20 keV. For such energetic PE's the initial stopping power, namely, the energy loss per unit distance, is quite small and increases greatly as they slow down. The distance a 20 keV PE travels is 6 microns. Thus by concentrating the x-rays in small regions separated by slightly more than 6 microns, the goal of separating the diffraction and damaged regions can be accomplished. Any improvement in controlling or reducing primary radiation damage would have major impact on all of macromolecular x-ray crystallography, e.g., opening new crystallography for very large structures, increasing structure resolution of standard sized crystals and obtaining useful structure information from very small platelet-shaped crystals. By reducing damage to crystals during x-ray crystallography, this instrumentation will speed up the accumulation of crystal structures and the understanding of structure-function relationships of biological macromolecules. The project is interdisciplinary, involving physicists and a biologist, and international, involving a physicist from Israel.