Uwe Müller and Gustavo Lima were recently awarded funding from Vetenskapsrådet for their project FragMAX. This project runs in collaboration with two Swedish companies, Astra Zeneca and SAROMICS BioStructures and the Lund University Protein Production Platform LP3. FragMAX aims to establish a fragment screening facility at MAX IV, which is an important tool for industrial drug discovery as well as probing the functional surfaces of proteins within a basic science approach.
Fragment-based drug discovery is becoming an increasingly important part of the drug discovery process. It is used after a researcher has discovered a drug target, such as a protein involved in cancer. The researchers would then crystallize the protein and screen many different low molecular weight fragments against it to see which ones bind and where. By looking at the structure of the fragments that bind to the target protein using X-ray crystallography, the researchers can get insights into how the structure of a potential drug could look like.
There are two exciting benefits to fragments screening in the drug discovery process. The first is the discovery of completely novel drugs. The probability that a molecule will bind to a protein target decreases with complexity. This means that screening with large molecules only works if you get an almost perfect candidate. By using small fragments, the chance of binding increases, meaning the researchers can look at many small molecule interactions and build up a larger drug candidate by using high throughput screening.
The second benefit is a reduced lead time to drug discovery. Fragment screening has the potential to shave research-intense months off the drug discovery process. These months would add a substantial cost to the drug discovery process and removing them could change the economics of drug discovery, making it cheaper and more efficient.
The key for the FragMAX project is to develop the infrastructure and competence at MAX IV to do fragment screening, as well as working with external partners to develop the best fragment library for the work that will be done at MAX IV.