u/arrestinbias

https://m.youtube.com/watch?v=xAJGUnjtl8o&t=545s

A few people here have followed and engaged with my previous posts about the ~700 million molecule virtual screen I’ve been running, so I wanted to share the next stage of the project.

After the initial large-scale screening and successive filtering steps, I’m down to roughly 200,000 compounds. At this point, rather than continuing to rank everything against a single receptor structure, I’ve been looking at an ensemble approach using multiple receptor conformations.
In this video I spend some time going through why I’m doing that, how I evaluated the different receptor structures using control compounds/decoys, and how I’m using that information to decide which conformations should contribute to the final filtering of the ~200k compounds.

The ultimate goal is to reduce some of the structural bias that comes from relying on one static receptor structure and hopefully end up with a more robust set of compounds to prioritize experimentally.

I’d also be interested in hearing how others here have approached ensemble docking / receptor-conformation selection, particularly when you have enough structures available that simply docking against all of them becomes computationally expensive.