Prediction on Binding Affinity of Nordentatin and Quercetin Against Anti-apoptotic BCL-2 Protein

• Published in: Journal of International Dental & Medical Research Vol. 11; no. 3; pp. 1116 - 1122
• Main Authors: Afriza, Dhona, Ichwan, Solachuddin J A, Suriyah, Wastuti Hidayati, Wahyuni, Fatma Sri, Yanwirasti, Tejo, Bimo A
• Format: Journal Article
• Language: English
• Published: Diyarbakir Ectodermal Dysplasia Group - Turkey 01.09.2018
• Subjects: Affinity; Anthraquinone; Apoptosis; Bcl-2 protein; Binding sites; Bioinformatics; Cancer; Cell survival; Crystallography; Electrostatic properties; Flavonoids; Free energy; Hydrogen; Hydrophobicity; Kinases; Ligands; Protein folding; Protein structure; Proteins; Quercetin; Software; Sulfonamides; United States > US
• ISSN: 1309-100X; 1309-100X

Bcl-2 is the most studied anti-apoptotic member, known to restrict apoptosis and facilitates the survival cell independently by promoting the division of cell.3 The protein is excessively expressed in a number of cancers and have been attributed to the resistance of cancer to conventional treatment.4 Inactivation of Bcl-2 restored the apoptosis function in cancer cells. [...]targeting Bcl2 2 been proposed as a promising anticancer strategy.5 Phytoconstituents, such as anthraquinone, coumarins, flavonoids, and terpenoids might serve as active therapeutic agents due to their wide range pharmacological effects, including anticancer.6 However, many of their molecular targets have not been completely understood. The hydrogen-bond of donors and acceptors, and the molecular mass are crucial parameters to the structure of protein target and ligand binding sites.20 The poor absorption or permeation of a compound is predicted more likely to bind when there are >5 hydrogen-bond donors, >10 hydrogen-bond acceptors, the molecular mass is >500, and calculated log P (CLog P) is >5.21,22 The docking protocol was validated by redocking n-heteroaryl sulfonamides to cocomplex Bcl-2 [PDB: 4IEH].23 The size and center of the coordinates in the grid box in molecular docking have to be validated to convince the binding of ligands ties to the binding pocket in the right conformation.16 The result showed that the redocking n-heteroaryl sulfonamides position was similar with the crystallographic position (Figure 1) indicating that the AutoDock docking parameters used are applicable to this system. Hydrogen binding is also assisted in protein stability, but the percentage of hydrogen binding is lower than hydrophobic interactions even for the smallest globular proteins.30 The role of hydrophobicity was approximately higher twice than in hydrogen binding of protein folding.31 The hydrophobic binding is the main factor involved in folding configuration equilibrium in many native proteins.30 Electrostatic interactions act in determining the binding affinity, structure, chemical characteristics, stability and the biological reactivity of proteins and nucleic acids. [...]both protein folding and protein-ligand binding process occurs when total Gibbs of free energy in system reduces.34,25 The negative binding energy maximum reflects the highest binding affinity between protein and ligand.