Targeting V347G Variant in NLRP1 Protein Causing Vitiligo with Morin and Kaempferol Flavonoids: A Computational Pipeline

Abstract Vitiligo is a chronic depigmenting condition marked by the progressive loss of functioning melanocytes, resulting in nonscaly, chalky‐white lesions on the skin. Vitiligo is caused by a complicated combination of genetic and environmental variables, with NLRP1 gene variants recognized as significant contributors to the condition. NLRP1 is an important factor in the construction of inflammasomes, which are major mediators immunological responses and can cause melanocyte death. This study investigates the effect of genetic variants in NLRP1 protein, specifically missense substitutions, in conferring susceptibility to vitiligo. The study used a variety of in silico methods such as PANTHER, MetaSNP, PhD‐SNP, SNAP, iSTable, iMutant Consurf, and more to assess the pathogenicity, stability, and biophysical features of these variations. The study examines the possible therapeutic benefits of natural substances Morin and Kaempferol on the activity of mutant NLRP1 proteins. Molecular docking and dynamics simulations demonstrated that Morin has a higher binding affinity to both native and mutant versions of NLRP1 than Kaempferol. These findings imply that these natural compounds could be used to treat vitiligo. However, additional chemical changes may be required to improve binding affinities and therapeutic efficacy. The findings highlight the potential of natural medications to target NLRP1 variations as a novel method to treat vitiligo and other autoimmune disorders.