An advanced data analysis platform for the crystallographic fragment screening (CFS) method is available for users and other partners of MAX IV. This web-based data analysis platform facilitates data processing, structure refinement, automated ligand fitting, multi dataset analysis, and even data visualization of CFS method experiments at the BioMAX beamline — bringing CFS project management to the next level.
Research on new pharmaceutical drugs is continuously prominent for public health concerns. The CFS method is critical within structure-based drug discovery that explores new pharmaceutically active compounds and helps researchers to discover potential protein functionalities. This method is complementary to traditional biophysical screening methods within a modern drug discovery process.
However, while conducting extensive CFS experiments, researchers were often preoccupied with the technicalities of massive data analysis and the building of multiple models to find “the needle in the haystack”. It’s because the processes, from the preparation of fragment-soaked protein crystals, primary raw data processing, up to ligand identification, were traditionally organized in a classical lab book style.
Determined to solve these challenges, a joint team from MAX IV, SAROMICS, Astra Zeneca, as well as the Lund Protein Production Platform (LP3) of Lund University, with the full support from Vetenskapsrådet and VINNOVA, developed an integrated, next level CFS project management and data analysis platform: FragMAXapp.
“FragMAXapp is a software platform, which connects the scientist to all relevant steps of a crystallographic fragment screening: from the generation of fragment-soaked protein crystals at LP3, the processing of hundreds of diffraction datasets, the structure solution, and refinements as well as ligand identification”, explained Uwe Mueller, the initiator of the FragMAX project.
Data analysis made easy
Within its central database, FragMAXapp can store hundreds of GB of metadata per experiment, extract the relevant metrics from those data, and present them either graphically or numerically. The web-based app is able to launch hundreds of data evaluations with just one click, thanks to MAX IV’s high-performance computing infrastructure.
As an integral tool to manage, process, analyze, and export fragment screening data, FragMAXapp provides remote access possibility by using VPN to reach the network. Users can even access the platform through iNEXT-Discovery. Besides that, FragMAXapp also offers connectivity to other beamline applications such as the ISPyB sample database and the MXCuBE experiment control software. Furthermore, the web-based app is equipped with project encryption when needed in the case of sensitive data handling.
“One has to say that the FragMAXapp is heavily motivated by the software XChemExplorer, which has been developed at the Diamond Light Source, UK. We regarded this as the gold standard for any future development”, explained Mueller.
Mueller stated that the team’s biggest challenge initially was to develop the platform. However, this was eventually overcome.
“I was delighted to see how Gustavo Lima was able to develop this software to what it is. And he did it very fast on top of it. The outcome of his developments exceeded by far what I described within the initial project proposal, which then led to the funding decision by VR”, explained Mueller.
Currently, MAX IV and HZB are working together to enable the software installation in Berlin.
“I would wish that FragMAXapp can be used for many screening campaigns and be further developed continuously. Another direction I am involved in from the HZB side is to make the software available to other fragment screening facilities, like the HZB”, explained Mueller.
FragMAX is a modular screening platform at the BioMAX beamline at MAX IV. It is meant to aid crystallographic fragment screening projects in all stages, among others: access to fragment libraries, experimental design assistance, sample production, data gathering, and data analysis—mainly used for new pharmaceutical drugs discovery. Read more about FragMAX here.
Lima, G. M. A., Jagudin, E., Talibov, V. O., Benz, L. S., Marullo, C., Barthel, T., Wollenhaupt, J., Weiss, M. S. & Mueller, U. FragMAXapp: crystallographic fragment-screening data-analysis and project-management system. (2021). Acta Cryst. D77, 799-808.