Identification of Anti-cancerous Drugs for The Mutated SNAP25 Protein Related to Brain Tumor through Structure-Based Virtual Screening Approach

Authors

  • SAMEER SHARMA Indian Academy Degree College - Autonomous

Keywords:

Anti-cancer, CADD, Drug Discovery, SBVS, Autodock

Abstract

Brain tumor is a formidable challenge for drug development, and drugs derived from many advanced technologies are being tested in clinical trials. Several researchers have already discovered anti-cancerous drugs that can be used for the treatment of brain tumors in adults and as well as children. SNAP25 (synaptosomal-associated protein of 25 kDa) is a membrane-binding protein in neurons and it is critical in neurotransmission for the fusion of plasma membrane and synaptic vesicle making it a prime target to address brain tumors. The SNAP-25 gene is responsible for personality disorders, schizophrenia, attention deficit, and hyperactivity disorder in human beings. It is recently discovered, that this protein is responsible for brain cancer as well. In the present research, 17 investigational and experimental anticancer drugs were selected from the PubChem and DrugBank databases to identify potential inhibitors with high stability to treat mutated SNAP25 protein. For this purpose, we have used the structure-based virtual screening (SBVS) technique wherein, the candidate molecules are computationally docked into the 3D structure of the biological target that is derived from biophysical methods, such as X-ray crystallography, NMR spectroscopy, cryo-electron microscopy, homology modeling, or molecular dynamics simulations. The docking was achieved in PyRx 0.8 software and the drugs were then ranked based on their predicted binding affinity or complementarity to the binding site. Based on the ligand binding energy, the top six compounds having greater inhibitory effects towards SNAP25 were selected and then visualized with Pymol and Biovia visualizers. The compound Crenolanib has better pharmacological properties and demonstrated higher binding affinities with the target protein. Therefore this Crenolanib docked confirmations were appraised for molecular dynamic simulations. The study concluded that the anticancer drug Crenolanib exerted inhibitory potential against the mutated protein SNAP-25 and therefore it can be exploited as a cancer modulator to address brian tumors.

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Published

16-01-2023

How to Cite

SHARMA, S. (2023). Identification of Anti-cancerous Drugs for The Mutated SNAP25 Protein Related to Brain Tumor through Structure-Based Virtual Screening Approach. Innovare Journal of Medical Sciences, 11(2). Retrieved from https://innovareacademics.in/journals/index.php/ijms/article/view/47146

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Original Article(s)