BIOPTIC B1 Ultra-High-Throughput Virtual Screening System Discovers LRRK2 Ligands in Vast Chemical Space.

ABSTRACT: The rapid expansion of chemical space presents significant challenges in identifying novel ligands for drug targets. Here, we introduce BIOPTIC B1, an ultra-high-throughput ligand-based virtual screening system capable of rapidly evaluating multi-billion-molecule libraries in minutes. In retrospective analyses across seven diverse drug targets, BIOPTIC B1 demonstrated performance comparable to state-of-the-art machine learning models, including Chemprop and Gradient Boosting. Prospectively, we applied BIOPTIC B1 to leucine-rich repeat kinase 2 (LRRK2), a high-priority drug target for Parkinson's disease. BIOPTIC B1 successfully identified multiple novel ligands binding both wild-type and G2019S-mutant LRRK2 with dissociation constants (K_d) as low as 110 nM, directly from the Ena

SUBMITTER: Vinogradov V 

PROVIDER: S-EPMC12529759 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature