Molecular Docking and Molecular Dynamics Simulation of Enzyme–Drug Interactions: In Silico and in Vitro Evaluation of Flavone as a Potential Inhibitor of Human Triose Phosphate Isomerase (TPI1)

Abstract

Other choices for comprehending chemical systems are offered by computational techniques, which produce information that is challenging, if not impossible, to gain from laboratory examination. Using computational methods like docking, it is simple to verify a compound's strength of binding in the active site after it has been constructed within such computer programs. Flavonoids are a vital component of many pharmacological, cosmetic, nutraceutical, and medicinal applications due to their various health-promoting qualities. This is mainly because of their ability to regulate the activity of crucial cellular enzymes and their anti-oxidative, anti-inflammatory, anti-carcinogenic, and anti-mutagenic properties.By concentrating just on the most likely compounds, computer-aided drug design (CADD) helps scientists save time and money on chemical and therapeutic testing. Our primary goal was to employ molecular docking and molecular docking simulation programs to investigate the inhibitory effect of flavonoid drugs toward the TPI1 enzyme.  This inhibitor might then be tested experimentally to stop the activity of the enzyme. Flavone were specifically selected to evaluate their binding capacities. This study also investigated the application of the flavone compound and its effect on serum samples from female breast cancer patients—breast cancer being the most common cancer among women, accounting for 22% of all malignant tumors. The enzyme triosephosphate isomerase (TPI1) has been identified as a potential oncogene and a biomarker in the serum of patients with breast cancer and other malignancies. Serum samples were collected and subjected to a multi-step partial purification process, including gel filtration, dialysis, and the use of ion-exchange resins (such as DEAE-cellulose and Sephadex G100). The purification results yielded an enzyme recovery rate of 41%, a purification factor of 1.55, and a specific activity of 0.36 U/mg. Kinetic analysis determined the optimal substrate concentration to be 5.5 mM, the Km value to be 11.11 mM, with a maximum velocity of 12.5 units/mL (Vmax). The enzyme showed maximal activity at 37°C with an ideal pH of 7, according to an analysis of the influence of different variables on the enzymatic reaction rate.