IMPROvER: The Integral Membrane Protein Stability Selector

We’re happy to share this recent open access publication out in Nature Scientific Reports: “IMPROvER the Integral Membrane Protein Stability Selector”, which was authored by one of our scientists, Dr Steven Harborne.

Membrane proteins are often intrinsically flexible, unstable and difficult to work with. One method to help make them less challenging, is to introduce mutations that reduce flexibility and stabilise them, but without removing protein activity. The difficulty is knowing which amino acid positions in a protein should be changed, and what to change them to. Traditionally, stabilising mutations have been found by a painstaking trial and error process where all positions of a protein are tested. IMPROvER is a software tool to help select where and what likely stabilising mutations are going to be, greatly improving efficiency.

The publication details how the software works, using a number of bioinformatic techniques to identify and rank potentially stabilising mutations in α-helical membrane proteins. Furthermore, three membrane protein target case studies are presented, showing that IMPROvER has a target dependent hit rate of 25-40%, where a hit is considered to be an increase in thermostability by at least 1.5˚C. This is in comparison to 7.6% that is expected if selections are made randomly in the protein.

IMPROvER is available freely to the academic community. Peak Proteins is also licensed to use IMPROvER for commercial aspects, and we’ve already had some successes with a tricky client GPCR (more detail to follow soon). So, if you have a difficult membrane protein expression and purification problem, please contact us, and we may be able to help!