Advances in High‐Throughput Crystallisation

Abstract

Abstract Molecular biologists attempt to understand the inner workings of the cell, the smallest unit of all life forms on earth. The constituents that perform cellular functions are the proteins, enzymes and nucleotides. A full appreciation of the chemical and biological functions of the cellular constituents, and therefore life itself, requires knowledge of their three‐dimensional structures. X‐ray crystallography is among the most powerful methods to derive structural information from biological macromolecules. Before the three‐dimensional structure of biological macromolecules can be determined by X‐ray crystallography, they have to be assembled into the regular and periodic arrangements, which define a crystal. Biological macromolecules are irregularly shaped and inherently flexible, which makes their crystallisation very difficult. It frequently implies the testing of many different sample variations under many hundred conditions. This is the reason for the establishment of automated high‐throughput crystallisation facilities. Key Concepts: Progress in the life sciences requires knowledge of the cellular processes at a molecular level. The principal components of the cell are proteins and nucleic acids. The three‐dimensional structures of the cellular components define their functions. X‐ray crystallography is the method of choice to determine the structure of biological macromolecules. Crystallisation of biological macromolecules for X‐ray crystallography requires the testing of hundreds to thousands of conditions. Automation supports many processes in molecular biology, by performing routine operations with the help of robotics. High‐throughput crystallisation has significantly improved success rates in crystallography through the rapid and comprehensive screening of many sample constructs under many different conditions.