Computer-aided drug discovery of potential inhibitors against fatty acid binding protein (FABP4) involved in colorectal adenocarcinoma
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Date
2025
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Publisher
UMT, Lhr
Abstract
Fatty acid binding protein (FABP4) is a novel therapeutic target protein overexpressed in colorectal adenocarcinoma (COAD), the most common subtype of colorectal cancer (CRC). Its mechanism has not been completed elucidated, yet it is known that it has been expressed and cause lipogenesis which support signaling pathways responsible for colorectal adenocarcinoma (COAD). This study aimed to discover lead compounds as novel inhibitors against Fatty acid binding protein (FABP4) through pharmacophore modeling and virtual screening using Pharmit server, retrieving compounds from PubChem and CHEMBL34 databases. These hits were evaluated based on drug likeness prediction, applying Lipinski rule of five, Veber’s rule for filtering and ADMET predictors. Finally, out of 1382 compounds, 314 compounds were further
narrow downed using molecular docking analysis against FABP4 to find out the compound with lowest S (score) with the selected protein. Based on S score, 10
compounds were shortlisted and subjected to further investigation using density functional theory (DFT) to find out the reactivity of compounds. Among these compounds, Compound-1 with PubChem Identifier (CID_145925339) having S score (-8.1) was selected as potential inhibitor and lead compound against FABP4. In the end, molecular dynamics (MD) simulation was run for determining the stability of the docked complex of ligand and protein. Post simulation analysis was done by analyzing root mean square deviation (RMSD), root mean square fluctuation (RMSF), hydrogen bond trajectory analysis and radius of gyration (Rg). Overall, this study concluded that Compound-1 (CID_145925339) can serve as a potential inhibitor against fatty acid binding protein.