Harnessing the Power of Machine Learning Guided Discovery of NLRP3 Inhibitors Towards the Effective Treatment of Rheumatoid Arthritis.

ABSTRACT: The NLRP3 inflammasome, plays a critical role in the pathogenesis of rheumatoid arthritis (RA) by activating inflammatory cytokines such as IL1β and IL18. Targeting NLRP3 has emerged as a promising therapeutic strategy for RA. In this study, a multidisciplinary approach combining machine learning, quantitative structure-activity relationship (QSAR) modeling, structure-activity landscape index (SALI), docking, molecular dynamics (MD), and molecular mechanics Poisson-Boltzmann surface area MM/PBSA assays was employed to identify novel NLRP3 inhibitors. The ChEMBL database was used to retrieve compounds with known IC₅₀ values to train machine learning (ML) models using the Lazy Predict package. After data pre-processing, 401 non-redundant structures were selected for exploratory da

SUBMITTER: Ilyas S 

PROVIDER: S-EPMC11719798 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature