In silico fragment-based discovery of CIB1-directed anti-tumor agents by FRASE-bot.

ABSTRACT: Chemical probes are an indispensable tool for translating biological discoveries into new therapies, though are increasingly difficult to identify since novel therapeutic targets are often hard-to-drug proteins. We introduce FRASE-based hit-finding robot (FRASE-bot), to expedite drug discovery for unconventional therapeutic targets. FRASE-bot mines available 3D structures of ligand-protein complexes to create a database of FRAgments in Structural Environments (FRASE). The FRASE database can be screened to identify structural environments similar to those in the target protein and seed the target structure with relevant ligand fragments. A neural network model is used to retain fragments with the highest likelihood of being native binders. The seeded fragments then inform ultra-large-scale

SUBMITTER: An Y 

PROVIDER: S-EPMC11219766 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature