CAREER: Experiencing the 5th Dimension, cis/trans and Z/E Isomerizations in Biomolecules

蛋白质是生命的催化剂。要使这种催化剂起作用，需要对催化剂本身的原子结构进行实质性的重组。通过实时观察原子长度尺度上的所有结构，从开始到结束直接跟踪催化反应将是理想的。时间分辨晶体学就是为了实现这一点而设计的。这项技术每秒可以记录多达100亿个x射线结构。时间分辨晶体学是一种真正的动力学方法。它研究四维、三维空间和时间的分子集合。为了确定一个全面的动力学机制，一个额外的参数，温度，将会改变。晶体学变成了五维的。本项目实现了五维晶体学，并利用它来研究两个重要的生物反应：光活性黄色蛋白中的光循环和胆道蛋白中的光-光开关反应。除此之外，这些研究将为合理设计具有新颜色的光学开关铺平道路，这些开关可用于生物物理研究中的许多应用。了解生物催化是生命科学中最重要的领域之一。时间分辨晶体学结合了动力学和结构测定。随着世界上最强的x射线源，用于硬x射线的自由电子激光器的出现，五维晶体学可以在速度和样品尺寸方面达到最大的完美。这将带来新的研究机会。为了吸引年轻的学者，PI将通过培训在PI实验室担任指导者的科学教师，向密尔沃基的高中介绍大分子晶体学。威斯康星大学密尔沃基分校生物物理学的广泛教育计划将吸引聪明的本科生和研究生参与正在进行的项目。对世界上最强的x射线源的多次访问将提供大量的实践机会。结果将通过PI的网页发布，这样任何人都可以体验到晶体学的第五维度。

Proteins are the catalysts of life. For such a catalyst to work, substantial reorganization of the atomic structure of the catalyst itself is required. It would be ideal to follow the catalytic reaction directly from the beginning to the end by looking at all the structures on the atomic length scale and in real time. Time-resolved crystallography is designed to achieve this. This technique is able to record up to 10 billion X-ray structures per second. Time-resolved crystallography is a true kinetic method. It investigates an ensemble of molecules in four dimensions, 3 space dimensions and the time. In order to determine a comprehensive kinetic mechanism, an additional parameter, the temperature, will be varied. Crystallography becomes five-dimensional. This project implements five-dimensional crystallography and uses it to investigate two important biological reactions: the photo-cycle in photoactive yellow protein and the photo-optical switching reaction in a biliprotein. Amongst other things, these investigations will pave the way for example for a rational design of optical switches with new colors that can be used for many applications in biophysical research.Understanding biological catalysis is one of the most important fields in the life sciences. Time-resolved crystallography unifies kinetic with structure determination. With the advent of the world's strongest X-ray sources, the free electron lasers for hard X-rays, five-dimensional crystallography can be brought to utmost perfection in terms of speed and smallness of specimen. This will open new research opportunities. To attract young academics, the PI will introduce macromolecular crystallography to Milwaukee's high schools by training science teachers who work as mentees in the PI's lab. A broad educational program in biophysics at the UW-Milwaukee will attract bright undergraduate and graduate students to be included in ongoing projects. Numerous trips to the world's strongest X-ray sources will give plenty of hands-on opportunities. Results will be distributed through the PI's web page so that anyone can experience the fifth dimension in crystallography.