Prediction of Aflatoxin-B1 (AFB1) Molecular Mechanism Network and Interaction to Oncoproteins Growth Factor in Hepatocellular Carcinoma

Abstract

Aflatoxin-B1 (AFB1) is a common contaminant for staple foods during the storage process. Chronic exposure to AFB1 is widely known to induce the development of hepatocellular carcinoma (HCC). However, there is a lack of understanding of AFBi role in HCC mechanism. This research aims to identify protein(s) in HCC that might interact with AFB1 and to predict the pathway effected by AFB1. Analyses were performed using bioinformatics tools. SMILES notation of AFB1 was submitted into Swiss Target Prediction. Interaction among predicted proteins were analyzed by using STRING. The 3D structure of target protein was constructed by homology modeling. Reverse docking was performed, and the result was ranked based on binding affinity score. Furthermore, protein interaction network was constructed and analyzed by using Cytoscape. Results showed that three protein groups were predicted as target of AFB1, such as kinases, phosphatases, and G protein-coupled receptor with probability of 46.7%, 20%, and 6.7%, respectively. Seven proteins of kinases were strongly related to HCC, including RAF1, MAPK1, MAPK3, AKT1, EGFR, GSK3B, and mTOR. Reverse docking considered the AKT1-AFB1 as the most potential complex with the lowest affinity score -10.2 kcal.mol-1. It has hydrophobic bonds in Trp80, Val270, Tyr272, Asp292, Thr211, Leu210, Leu264, and Lys268 residues, whereas hydrogen bond in Ser205 residues. Moreover, further analysis demonstrated that interaction of AKT1-AFB1 is related to the metastasis pathway in HCC mechanism.

The Potential of Antivirus Compounds in Gletang (Tridax procumbens Linn.) in Inhibiting 3CLpro Receptor of SARS-CoV-2 Virus by In Silico

“…Interaction of van der Waals showed in light green circle of amino acid residue. 21 The 3CLpro receptor was composed with 1224 amino acid residues that folded and coiled to form a protein with a three-dimensional structure. Amino acids were formed from a carboxyl group and an amino group connected by an asymmetric carbon atom.…”

“…Hydrogen bond is the main interaction on the drug molecule, showed with the distance of interaction was smaller than other interaction. 21 According to statement of Friesner et al and Listyani et al that the smaller the interaction distance between the ligand and the receptor, the stronger the interaction that occurs. 20,23 Hydrogen bond interactions occur through the replacement of water molecules in proteins by ligands, which can increase entropy to achieve stability in the sequence of amino acid residues.…”

“…20,23 Hydrogen bond interactions occur through the replacement of water molecules in proteins by ligands, which can increase entropy to achieve stability in the sequence of amino acid residues. 21,23 In contrary, hydrophobic bonds occur due to the presence of nonpolar amino acid residues that bind to ligands, in the form of covalent bonds between two carbon atoms (pi-pi stacked) or between carbon and hydrogen atoms (pi-alkyl). 21 Nonpolar molecules will gather to form aggregates in an aqueous environment which reduces entropy because water cannot form hydrogen bonds with nonpolar molecules.…”

“…21,23 In contrary, hydrophobic bonds occur due to the presence of nonpolar amino acid residues that bind to ligands, in the form of covalent bonds between two carbon atoms (pi-pi stacked) or between carbon and hydrogen atoms (pi-alkyl). 21 Nonpolar molecules will gather to form aggregates in an aqueous environment which reduces entropy because water cannot form hydrogen bonds with nonpolar molecules. 25 The target of in-silico determination of drug compounds has a combination of hydrophobic interactions with one to three hydrogen bonds to increase the potential for stability in laboratory-scale testing.…”

“…This electrostatic interaction can provide a coordinate direction for the ligand to move towards the protein with greater force if it is positively charged and maintain the stability of the ligand on the receptor. 21,23 While, van der Waals interactions can occur when two atoms are sufficiently close together, in all types of polar and nonpolar molecules. The interaction causes random fluctuations in the electron distribution.…”