A Beginner’s Guide to Macromolecular Crystallisation

Protein Structure Determination

Being able to determine and visualise the atomic structures of proteins is of invaluable help not only in studying their function but also in aiding the rational design of new potential drugs that target them. One of the main methods of obtaining such protein structures is by X-ray crystallography. As the name suggests this method critically hinges on the ability to generate well-ordered 3D crystals of the proteins of interest and this is generally rate limiting of the process. As there is currently no way to predict a priori the conditions required to generate such crystals from just sequence information it relies instead on an empirical trial and error approach and as such it has historically obtained the reputation of being somewhat of a black art to the uninitiated.

Introduction to the Crystallisation of Macromolecules.

Although there is a vast amount of literature available on methodologies of protein crystallisation including the classic “Crystallisation of Biological Macromolecules” by Alexander McPherson (Cold Spring Harbor Laboratory Press, 1999) there is still a need for a good brief introduction for non-experts who may be interested in the possibility of crystallising their target of interest.

A great example of such an overview was recently published in The Biochemist entitled “A beginner’s guide to macromolecular crystallization” (Fabrice Gorrec; A beginner’s guide to macromolecular crystallization. Biochem (Lond) 3 February 2021; 43 (1): 36–43. doi: https://doi.org/10.1042/bio_2020_108). This is a very well-written albeit brief review that clearly explains many of the concepts and practical issues involved in the crystallisation of macromolecules and answers many of the initial questions often asked by clients when considering the crystallisation of potential targets.

If this great beginners guide “peak’s” your interest in the crystallisation and subsequent structure determination of your protein of interest then please get in touch with us at info@peakproteins.com where we will be happy to discuss the options available.