Radiation damage to ligands and inhibitors in protein crystal structures
What is it about?
Protein-inhibitor crystal structures are important in the design of new drugs as they visualise the binding of the drug to the target protein. To do this we crystallise the protein with its inhibitor and illuminate the crystals with intense X-ray radiation. From the X-ray diffraction pattern of the crystal we can calculate what the protein-inhibitor structure looks like. However, the intense X-rays damage our samples during data collection. We have shown that the X-rays specifically damage protein-bound inhibitors that contain halogen atoms such as chlorine and bromine.
Why is it important?
The intense X-rays used to determine protein-inhibitor structures specifically cause breakage of carbon-halogen atoms in the protein-bound inhibitors and can therefore affect how we interpret the interactions that the inhibitor makes with the protein. This is important because many drugs and candidate drugs contain halogen atoms such as chlorine as they are very good at making specific interactions with the protein. Our study will help to better understand the damage to our protein-ligand crystals, how this affects the data we collect, and hopefully helps to ensure we can provide the best quality data for the design of new drugs.