Computational Study of Asian Propolis Compounds as Potential Anti-Type 2 Diabetes Mellitus Agents by Using Inverse Virtual Screening with the DIA-DB Web Server,Tanimoto Similarity Analysis,and Molecular Dynamic Simulation

Propolis contains a wide range of pharmacological activities because of their various bioactive compounds. The beneficial effect of propolis is interesting for treating type-2 diabetes mellitus (T2DM) owing to dysregulation of multiple metabolic processes. In this study, 275 of 658 Asian propolis compounds were evaluated as potential anti-T2DM agents using the DIA-DB web server towards 18 known anti-diabetes protein targets. More than 20% of all compounds could bind to more than five diabetes targets with high binding affinity (<−9.0 kcal/mol). Filtering with physicochemical and pharmacokinetic properties, including ADMET parameters, 12 compounds were identified as potential anti-T2DM with favorable ADMET properties. Six of those compounds, (2R)-7,4′-dihydroxy-5-methoxy-8-methylflavone; (RR)-(+)-3′-senecioylkhellactone; 2′,4′,6′-trihydroxy chalcone; alpinetin; pinobanksin-3-O-butyrate; and pinocembrin-5-methyl ether were first reported as anti-T2DM agents. We identified the significant T2DM targets of Asian propolis, namely retinol-binding protein-4 (RBP4) and aldose reductase (AKR1B1) that have important roles in insulin sensitivity and diabetes complication, respectively. Molecular dynamic simulations showed stable interaction of selected propolis compounds in the active site of RBP4 and AKR1B1. These findings suggest that Asian propolis compound may be effective for treatment of T2DM by targeting RBP4 and AKR1B1.     

Applications of Crank-Nicolson method with ADI in laser transformation hardening

A two-dimensional numerical solution for pulsed laser transformation hardening is developed using the finite difference method (FDM). The FDM has been developed using Crank-Nicolson scheme which solved by using alternating-direction implicit method. If this present model was compared to the analytical solution, then the Crank-Nicolson scheme showed better results in terms of accuracy, consistency, stability, convergence, and performance than to the explicit scheme. The longer heating duration, higher laser beam intensity, and greater number of pulse had influences on increasing the maximum temperature. The repetitive heating had influences on extending the heat duration and increasing the initial temperature of domain. The shorter cooling duration in repetitive pulse produced higher maximum temperature. The thinner material’s thickness increased the cooling rate, which finally increased the possibility of austenite to transform into martensite phase. In addition, it was also found that the higher maximum temperature always reduced the cooling rate value when temperature cools down toward to the starting temperature of martensite formation. It reduced the possibility of martensite formation. It was also seen that the heat was conducted more effective to the axial direction than to the radial direction.