scholarly journals Structure-Based Virtual Screening and Molecular Dynamic Simulation Studies to Identify Novel Cytochrome bc1 Inhibitors as Antimalarial Agents

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Rahul P. Gangwal ◽  
Gaurao V. Dhoke ◽  
Mangesh V. Damre ◽  
Kanchan Khandelwal ◽  
Abhay T. Sangamwar

Cytochrome bc1 (EC 1.10.2.2, bc1) is an essential component of the cellular respiratory chain, which catalyzes electron transfer from quinol to cytochrome c and concomitantly the translocation of protons across the membrane. It has been identified as a promising target in malaria parasites. The structure-based pharmacophore modelling and molecular dynamic simulation approach have been employed to identify novel inhibitors of cytochrome bc1. The best structure-based pharmacophore hypothesis (Hypo1) consists of one hydrogen bond acceptor (HBA), one general hydrophobic (HY), and two hydrophobic aromatic features (HYAr). Further, hydrogen interactions and hydrophobic interactions of known potent inhibitors with cytochrome bc1 were compared with Hypo1, which showed that the Hypo1 has good predictive ability. The validated Hypo1 was used to screen the chemical databases. The hits obtained were subsequently subjected to the molecular docking analysis to identify false-positive hits. Moreover, the molecular docking results were further validated by molecular dynamics simulations. Binding-free energy analysis using MM-GBSA method reveals that the van der Waals interactions and the electrostatic energy provide the basis for favorable absolute free energy of the complex. The five virtual hits were identified as possible candidates for the designing of potent cytochrome bc1 inhibitors.

2021 ◽  
Vol 12 (1) ◽  
pp. 44-52
Author(s):  
Neni Frimayanti ◽  
Musyirna Rahmah Nasution ◽  
Elsa Etavianti

Zika virus caused of the emerging infections characterized by fever, Guillain-Barré syndrome (GBS) for adults. In the current work, we aimed to study the binding orientation of 1,5-benzothiazepine compounds as new potential agent against Zika virus inhibitor through molecular docking and molecular dynamic simulation. Since, 1-5-Benzothiazepines are particular interest for drug discovery and they also has some biological activities. However, their antiviral activities and in silico studies of the binding to their biological targets have not been extensively investigated. Molecular docking study of 1,5-benzothiazepine chalcone derivatives compounds with protein target 5GJB (PDB ID) and this protein was taken from the crystallographic structure. In this study, twelve 1,5-benzothiazepine chalcone derivative compounds were docked to the protein with the grid box along x, y and z radius of 26.85, 28.17 and 24.43 Å, respectively. Suramin was used as positive control. Thus, it can be used as a reference for design new inhibitors for Zika virus helicase. Based on the docking results, it is observed that compounds MA3 and MA8 are estimated to have activity as inhibitors for Zika virus helicase with binding free energy values of -4.6490 and -4.9291 kcal/mol, respectively. MA3 and MA8 were also stable during the MD simulations with the hydrogen bonding are still maintained before and after MD simulation. Furthermore, both of these compounds can be used an early stage for drug design and drug delivery process.


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