In Silico Molecular Docking Study Of A Benzoquinone Against Proangiogenic And Metastatic Colorectal Proteins

Krishnan, Meenaahsree (2022) In Silico Molecular Docking Study Of A Benzoquinone Against Proangiogenic And Metastatic Colorectal Proteins. [Project Paper] (Submitted)

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Abstract

Angiogenesis is an important component in metastatic pathway. Through the blood vessel formed by angiogenesis, the tumor cells exit the primary site and enters the blood circulation to secondary sites and this mechanism is known as metastasis. There are multiple signalling pathways for colorectal cancer initiation and progression and the proteins involved in these pathways are metastatic proteins that is responsible for the metastasis of colorectal cancer (CRC). 2- methoxy-6-undecyl-1,4-benzoquinone (BQ) is an anti-angiogenic compound isolated from Ardisia crispa root hexane extract (ACRH), which was reported to suppress various excessive angiogenesis related disorders including cancer. This study is to investigate the binding affinity of BQ with the proangiogenic and metastatic CRC proteins which are vascular endothelial growth factor receptor 2 (VEGFR2), phosphoinositide 3-kinase (PI3K), protein kinase B also known as AKT, v-raf murine sarcoma viral oncogene homolog B1 (BRAF), kirsten rat sarcoma virus (KRAS) and extracellular signal-regulated kinase (ERK). The involvement of the mentioned proteins with BQ was determined via in silico study. The protein structure was retrieved from Protein Data Bank (PDB). The literature for the structure provided in PDB was studied, the binding site and binding residue of the specific protein was identified. Then, the 3D structure of the protein and BQ was prepared using AutoDock4 software. The coordinate of the binding site in the protein was located using CB-Dock function. The coordinate was inputted in the Command Prompt and run using AutoDock Vina. The molecular docking process was run by AutoDock Vina and the result was given in the order of lowest to highest binding affinity. The interaction of BQ and the formation of bonds with the protein was viewed using PyMol. BQ was found to bind to all the proteins tested. The binding affinity of BQ with VEGFR2 is -7.6 kcal/mol, with PI3K is -10.1 kcal/mol, with AKT is -12.1 kcal/mol, with BRAF is -6.3 kcal/mol, with KRAS is -10.3 kcal/mol and with ERK is -9.0 kcal/mol. The best binding energy in docking is in the range from -8.0 kcal/mol to -11.71 kcal/mol. According to this range, it is shown that AKT, KRAS, PI3K and ERK has the best binding energy. AKT has the lowest binding energy which means it has the highest stability. The proposed pathway of BQ is mediated via suppression of VEGFR which in turn suppressed angiogenesis. BQ also suppressed PI3K, KRAS, BRAF, ERK and AKT by suppressing cell proliferation, growth and survival, respectively . However, BQ need to be studied further for more details about the inhibition. Binding of BQ with these proteins indicated that BQ suppressed the CRC development via suppression of RAS related pathway including the mitogen activated protein kinase (MAPK) pathway and PI3K/AKT pathways. MAPK pathway is one of the pathways involved in the chromosomal instability pathway and both MAPK and PI3K/AKT pathway is involved in the CpG island methylator phenotype (CIMP) pathway.

Item Type:	Project Paper
Faculty:	Faculty of Medicine and Health Science
Depositing User:	Ms. Nor Safa'aton Saidin
Date Deposited:	22 Aug 2023 06:34
Last Modified:	22 Aug 2023 06:34
URI:	http://psaspb.upm.edu.my/id/eprint/1360

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