CACHE Benchmarking Event 1
HOW IT WORKS
Each challenge will focus on a new protein target representing one of five possible challenges in hit-finding, based on the type of data available:
- Protein structure in complex with a small molecule, some structure-activity relationship (SAR)
- Protein structure in complex with a small molecule, no SAR
- Apo protein structure
- No experimentally determined protein structure, some SAR
- No experimentally determined protein structure, no SAR
For each challenge, participants will be invited to use their computational methods to find hits (drug-like molecules) for a protein target selected by CACHE. CACHE will procure the molecules from commercial vendors and test them experimentally with two rigorous binding assays. Compounds from de novo design methods will be procured by participants [details]. The purity and solubility of active molecules will also be evaluated experimentally. CACHE will provide each participant with the experimental protein binding data for their prediction. Using this knowledge, participants may predict a second round of molecules that will be experimentally tested by CACHE. Additionally, the structures of all selected molecules, but not their activity, will be made available to all participants who will be asked to use their computational method to identify hits. The final evaluation process will incorporate:
- experimental hit rate
- affinity and physico-chemical properties of the hits from a participant’s selection
- rank-ordering of compounds pooled from all participants.
- A panel of experienced medicinal chemists will also comment on the hits.
Participants will be asked to disclose their approaches in sufficient detail to enable an expert in the area to understand the methodology while computational algorithms can remain proprietary. At the end of the competition, all chemical structures and associated activity from all participants will be disclosed to the public. Participants who had elected to be anonymous will have the choice to disclose their identity at any time.
- Short Name: #CACHEBenchmarkingEvent1
- Created on: November 25, 2021
- Last update: July 25, 2022