AlphaFold2 structures guide prospective ligand discovery
University of California, San Francisco · Rockefeller University · +8 more institutions
Abstract
AlphaFold2 (AF2) models have had wide impact but mixed success in retrospective ligand recognition. We prospectively docked large libraries against unrefined AF2 models of the σ 2 and serotonin 2A (5-HT2A) receptors, testing hundreds of new molecules and comparing results with those obtained from docking against the experimental structures. Hit rates were high and similar for the experimental and AF2 structures, as were affinities. Success in docking against the AF2 models was achieved despite differences between orthosteric residue conformations in the AF2 models and the experimental structures. Determination of the cryo–electron microscopy structure for one of the more potent 5-HT2A ligands from the AF2…
Citation impact
- FWCI
- 28.74
- Percentile
- 100%
- References
- 86
Authors
21- JLJiankun LyuCorresponding
University of California, San Francisco, Rockefeller University
- NJNicholas J. KapolkaCorresponding
University of North Carolina at Chapel Hill
- RHRyan H. GumpperCorresponding
University of North Carolina at Chapel Hill
- AAAssaf AlonCorresponding
Harvard University, Boston VA Research Institute
- LWLiang WangCorresponding
Stanford University
Topics & keywords
- Docking (animal)
- Computational biology
- Affinities
- Chemistry
- Stereochemistry
- Ligand (biochemistry)
- Amino acid residue
- Receptor
- Affordable and clean energy