Functionally active modulators targeting the LRRK2 WD40 repeat domain identified by FRASE-bot in CACHE Challenge #1.

ABSTRACT: Critical Assessment of Computational Hit-Finding Experiments (CACHE) Challenges emerged as real-life stress tests for computational hit-finding strategies. In CACHE Challenge #1, 23 participants contributed their original workflows to identify small-molecule ligands for the WD40 repeat (WDR) of LRRK2, a promising Parkinson's target. We applied the FRASE-based hit-finding robot (FRASE-bot), a platform for interaction-based screening allowing a drastic reduction of the explorable chemical space and a concurrent detection of putative ligand-binding sites. In two screening rounds, 84 compounds were procured for experimental testing and 8 were confirmed to bind LRRK2-WDR with dissociation constants (K _d) ranging from 3 to 41 μM. To investigate the functional effect of WDR liga

SUBMITTER: Mettu A 

PROVIDER: S-EPMC11770807 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature