Chemoinformatics approach to identify novel inhibitors for obesity associated proteins

Abstract

newline The study aims to identify candidate genes targeting for obesity and potential natural anti-obesity compounds. RNA Seq analysis was carried out for 258 obese and 55 lean dataset samples obtained from NCBI GEO database The differentially gene expression studies DEGs revealed that 1971 upregulated and 615 downregulated with log2FC greater than equal to 2 point 5 and p value less than 0 point 05 Gene enrichment analysis highlighted obesity related pathways Protein protein interaction network analysis in Cytoscape revealed dense clusters including Pancreatic Lipase PNLIP and Fat mass and Obesity associated proteins FTO as candidate genes The Anti obesity compound database AOCD was created with 349 compounds from natural sources targeting pancreatic lipase PL appetite suppression AS and adipogenesis AD Further database compounds were analysed for cheminformatics studies and showed that Pancreatic lipase dataset exhibited highest structural diversity, scaffold diversity and fingerprint diversity among other two datasets Pancreatic lipase PL was prioritized with virtual screening of 126 plant derived and 1110 marine algal compounds Compounds with favourable binding affinities underwent Lipinskis property and toxicity prediction yielding 38 non toxic compounds Molecular docking and dynamics simulations identified BC010 7S 11S 12S 14R 4 14 dimethoxyamentol from brown algae Cystophora fibrosa as a promising pancreatic lipase inhibitor Similarly Fat mass and obesity associated protein FTO was studied with virtual screening and molecular dynamics leading to BT012 24and#949; hydroperoxyl 6and#946; hydroxy 24 ethylcholesta 4 28 29 dien 3 one an oxygenated fucosterol from brown alga Turbinaria conoides RL074 2 hydroxyluzofuranone B and RL442 10 acetoxyangasiol from marine red alga Laurencia sp exhibited potential anti-obesity lead compounds targeting FTO protein This integrated approach holds potential for accelerating anti obesity drug discovery from natural resources