Powder Diffraction Methods for Membrane Protein Structure Determination

膜蛋白占人类和其他真核生物基因组编码的所有蛋白质的很大比例，是当今市场上销售的所有药物的靶标。了解它们的三维结构对于了解它们的功能以及开发治疗疾病的新药很重要。蛋白质X射线结晶学研究提供了这样的结构信息，它需要蛋白质有序的、大的单晶。然而，目前膜蛋白结构测定的主要障碍之一是生产适合单晶研究的大小和质量的晶体的能力。虽然通常可以产生许多更小的晶体，但还没有开发出一种方法来利用这些晶体来确定膜蛋白的结构。该项目的目的是开发确定膜蛋白结构所需的方法和工具，该方法和工具不是基于单晶样品，而是基于使用粉末衍射技术的非常小的(微晶)束样品。

Membrane proteins comprise a large proportion of all the proteins coded by human and other eukaryotic genomes, and are the targets of more than one-half of all the pharmaceutical drugs marketed today. Knowledge of their three-dimensional structure is important for understanding how they function, and for the development of new drugs for the treatment of diseases. Protein X-ray crystallographic studies, which require well-ordered, large single crystals of the protein, provide such structural information. However, one of the major obstacles to membrane protein structure determinations currently is the ability to produce crystals of a size and quality suitable for single crystal studies. Although often many much smaller crystals can be produced, there has yet to be a method developed to utilise these for the determination of the structure of membrane proteins. The aim of this project is to develop both the methodology and tools necessary to determine the structure of membrane proteins based on samples not of single crystals, but of bunches of very small (microcrystals) using powder diffraction techniques.