Cache: Utilizing ultra-large library screening in Rosetta to identify novel binders of the WD-repeat domain of Leucine-Rich Repeat Kinase 2.

ABSTRACT: In this study, we present a pipeline for identifying novel ligands targeting the Tryptophan-Aspartate-Repeat domain 40 (WDR40) of Leucine-Rich Repeat Kinase 2 (LRRK2), a protein associated with Parkinson's disease, as part of the first Critical Assessment of Computational Hit-finding Experiments (CACHE) challenge, a blind benchmark experiment for drug discovery. Mutations in this protein are the most common genetic cause of familial Parkinson's disease, yet this target remains understudied. We conducted an ultra-large library screening (ULLS) of the Enamine REAL space using a newly developed evolutionary algorithm, RosettaEvolutionaryLigand (REvoLd), which allows for efficient screening of combinatorial compound libraries. The protocol involved refining the target structure with molecular

SUBMITTER: Liessmann F 

PROVIDER: S-EPMC12465524 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature