Study on accuracy of X-ray crystallographic data
A study undertaken by Dr Bojan Zagrovic and colleagues has sought to find out how correctly current programmes for the analysis of X-ray crystallographic data capture a protein’s structure and its dynamics. Using a Starting Grant from the European Research Council (ERC), Zagrovic, PhD student Antonija Kuzmanic, and Dr Navraj S. Pannu from Leiden University in the Netherlands, used computer simulation to build a protein crystal and analysed it by the methods of X-ray crystallography, before using standard software programs to capture the protein’s features from crystallographic data.
This allowed the team to test if the way crystallographic data is currently analysed ‘sees’ what’s really there. Kuzmanic explained: “We were really surprised to find that current software programmes, used to predict a protein’s structure from X-ray crystallography data, underestimates the level of dynamics – so how much each atom can wiggle around in its position – by up to six fold.”
Garib Murshudov of the University of Cambridge, UK, structural biologist and one of the examiners of Kuzmanic’s PhD thesis, wrote: “This is my favourite chapter, it is inspirational…it clearly shows that it is necessary to design new ways to describe protein dynamics in crystals.”
More accurate ways to interpret X-ray crystallography data and determine the dynamics of a protein will not only give a clearer and a more realistic picture of what the protein looks like in nature, but will also help to develop medicines that can modify the protein’s function more accurately and more potently.
