Using AlphaFold protein models for structure-based virtual screening of chemical libraries

This webinar is based on Albert and colleagues recent study exploring the use of AlphaFold-predicted protein structures for drug discovery against Chagas disease, a neglected tropical disease caused by the parasite Trypanosoma cruzi. The study used AlphaFold-predicted models of T. cruzi proteins to carry out a structure-based virtual screening of approximately 30,000 compounds. From this screening, top-ranked candidates were selected for experimental testing, and two already approved drugs showed significant specific antiparasitic activity. These results illustrated how AlphaFold-based virtual screening can support drug discovery efforts and accelerate the identification of new compounds against neglected tropical diseases, where the absence of experimentally determined structures is problematic.

Building on this experience, the webinar will walk through how AlphaFold can be applied to structure-based drug discovery more broadly, using Chagas disease study as an example. It will briefly introduce AlphaFold, covering its confidence metrics and where to download or generate predicted models. From there, the webinar will show the steps needed for running a virtual screening campaign: predicting and assessing binding pockets, downloading chemical libraries, tools for molecular docking, and processing and interpreting the resulting data. Throughout, a particular attention will be given to the caveats and limitations of using predicted rather than experimentally determined structures for docking, drawing on the challenges encountered in their study. The webinar will close by discussing what to keep in mind when adapting this workflow to other cases.

This event is part of a broader webinar series on user cases of the AlphaFold resources. For more information about the series and its webinars, please visit the following link: AlphaFold in practice: research use cases | EMBL-EBI Training

Who is this course for?

PhD students, early-career researchers, and other professionals interested in drug discovery (particularly in the field of neglected tropical diseases) who want to incorporate AlphaFold into their projects.

Outcomes

By the end of the webinar, you will be able to:

• Explain what AlphaFold is and interpret its key confidence metrics.
• Locate and download AlphaFold-predicted structural models.
• Predict and assess candidate binding pockets on a predicted structure.
• Use docking tools to screen compounds against a predicted structure.
• Process and interpret virtual screening results to prioritise candidate compounds.
• Know the limitations of using predicted structures in virtual screening campaigns.

This webinar, hosted on Zoom Webinar, is free to attend, but you need to register for a place beforehand, using the 'Register' button. Once registered, you will receive a confirmation email with a link to join the webinar.

The webinar will be recorded, and the recording will be made available on this page one day after the event. Please note that we do not issue certificates of attendance for our webinars. However, you will receive an email from our Zoom account confirming your participation a day after the event