In-Silico Approach for Potential Drug Target in Human Mutant Complex with Nadph and AG-881 Inhibitor
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Date
2025
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Journal of Emerging Technologies and Innovative Research (JETIR)
Abstract
The drug discovery has undergone a significant transformation with the advent of computational approaches, enabling rapid identification and evaluation of potential therapeutic candidates. In-silico methods such as molecular docking, structural stability analysis, and toxicity prediction have become essential tools for exploring drug-target interactions. This study employs a computational approach to investigate potential drug targets in a human mutant complex bound to NADPH and AG-881 (Vorasidenib) inhibitor, with a particular focus on two promising compounds: Tovorafenib and Curcumin. Mutations in key regulatory proteins often lead to structural and functional alterations, which can contribute to the progression of various diseases, including cancer and metabolic disorders. Understanding how these mutations influence drug binding is crucial for designing effective targeted therapies. AG-881 is known for its selective inhibition of mutant enzymes, but alternative compounds such as Tovorafenib and Curcumin could provide new therapeutic avenues. Tovorafenib, a kinase inhibitor, has demonstrated efficacy in targeting oncogenic mutations, particularly in RAF kinase-driven malignancies, while Curcumin, a naturally occurring polyphenol, exhibits potent anti-inflammatory, antioxidant, and anticancer properties. Despite these promising attributes, the binding efficiency, stability, and toxicity profiles of these compounds in the context of the studied mutant complex remain unexplored. To evaluate their potential, molecular docking was performed using CB-Dock, an automated docking tool that predicts ligand binding sites and ranks interactions based on binding affinity. Structural stability analysis was conducted using PyMOL, where root mean square deviation (RMSD) calculations were used to assess conformational changes and the stability of the protein-ligand complexes. Additionally, the toxicity profiles of Tovorafenib and Curcumin were predicted using toxicity identification tools, which evaluates hepatotoxicity, carcinogenicity, mutagenicity, and overall drug-likeness. This study aims to determine the binding affinities of Tovorafenib and Curcumin with the mutant complex, analyze their impact on structural stability, and compare their toxicity profiles. By integrating these computational techniques, we aim to provide insights into the feasibility of repurposing these compounds for potential therapeutic applications. The results of this study could contribute to the ongoing efforts in precision medicine by identifying promising drug candidates that warrant further experimental validation through in-vitro and in-vivo studies. Leveraging in-silico approaches for drug discovery enhances our ability to identify novel treatments efficiently, reducing the time and cost associated with traditional drug development methods [1, 2, 3, 4 ,5].
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Keywords
Molecular docking, binding affinity, Tovorafenib, pharmacophore modelling, structural Analysis, AG-881 inhibitor