Docking-Based Virtual Screening and Molecular Dynamics Simulations of Quercetin Analogs as Enoyl-Acyl Carrier Protein Reductase (InhA) Inhibitors of Mycobacterium tuberculosis

Abstract

The emergence of multidrug-resistant Mycobacterium tuberculosis (MTB) has become a major problem in treating tuberculosis (TB) and shows the need to develop new and efficient drugs for better TB control. This study aimed to use in silico techniques to discover potential inhibitors to the Enoyl-[acyl-carrier-protein] reductase (InhA), which controls mycobacterial cell wall construction. Initially, 391 quercetin analogs present in the KNApSAck_3D database were selected, filters were sequentially applied by docking-based virtual screening. After recategorizing the variables (bond energy prediction and molecular interaction, including hydrogen bond and hydrophobic bond), compounds C00013874, C00006532, and C00013887 were selected as hit ligands. These compounds showed great hydrophobic contributions, and for each hit ligand, 100 ns of molecular dynamic simulations were performed, and the binding free energy was calculated. C00013874 demonstrated the greatest capacity for the InhA enzyme inhibition with ΔGbind = −148.651 kcal/mol compare to NAD (native ligand) presented a ΔGbind = −87.570 kcal/mol. These data are preliminary studies and might be a suitable candidate for further experimental analysis.

High throughput screening of a new fluorescent G-quadruplex ligand having telomerase inhibitory activity in human A549 cells

“…The best ligand as observed from the result is ZINC ID:05220992 (named as C-992) which was used for experimental validation. Several reports showed that using idock score people screened inhibitor (idock score≤ -8 kcal/mol) molecules against various receptors and worked well as per experimental validation report [27,28]. In this context, our screened compound showing a better idock score and RF score (-10.17 kcal/mol, 6.22 pKd).…”

Active Antialopecia Chemical Identification of Merremia peltata Leaves and Computational Study toward Androgen Receptor Using Molecular Docking and Molecular Dynamic Simulation

“…Meanwhile, the average RMSD fluctuations for each system, namely, minoxidil, finasteride, and bufotalinin, were 0.206, 0.203, and 0.211, respectively. The average RMSD showed that bufotalinin had the lowest fluctuation compared to the reference ligand, which indicates that the ligand has reached a stable conformation that binds to the protein [ 29 ]. The amino acid fluctuations of the two receptor complex systems calculated by RMSF showed the same pattern in all regions.…”

“…The SASA of the androgen receptor–ligand complex on the graph for bufotalinin showed similar fluctuations, which were higher than those for minoxidil and finasteride; the average values for minoxidil, finasteride, and bufotalinin were 120.13, 115.93, and 117.96 nm 2 , respectively. A low SASA value indicates an increasingly stable complex system [ 29 ]. This analysis correlated with that of the RMSD value, which indicated that bufotalinin had better stability at the androgen receptor than minoxidil and finasteride.…”

Searching of Novel Herbicides for Paddy Field Weed Management—A Case Study with Acetyl-CoA Carboxylase

“…Moreover, the 2D projection plot of PCA is another method to illustrate the dynamics of a protein in the essential subspace of the system [76]. Noteworthily, the protein-ligand system occupying less space was more stable, whereas the largely occupied system was less stable [77]. From Figure 8c, we observed that the overall motion of the ACCase-FPPE complex was confined within the eigenvalues ranging from −18 to 13 nm and −9 to 18 nm along with the projection of eigenvector1 and eigenvector2.…”