Exploring novel natural compound inhibitors for Parkinsonian receptor (DJ1) by homology modeling, molecular docking and MD simulations

2021 ◽  
Author(s):  
S. Vijayakumar ◽  
S. Rajalakshmi
Keyword(s):  
Molecular Docking ◽  
Homology Modeling ◽  
Natural Compound ◽  
Md Simulations

A comprehensive in silico study towards understanding the inhibitory mechanism of Lactoperoxidase by Dapsone and Propofol

2020 ◽  
Vol 16 ◽  
Author(s):  
Rameez Jabeer Khan ◽  
Rajat Kumar Jha ◽  
Gizachew Muluneh Amera ◽  
Jayaraman Muthukumaran ◽  
Rashmi Prabha Singh ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Md Simulation ◽  
Binding Free Energy ◽  
Protoporphyrin Ix ◽  
Md Simulations ◽  
Prosthetic Group ◽  
Drug Molecules ◽  
Group A ◽  
Complex Forms ◽  
Covalently Linked

Introduction: Lactoperoxidase (LPO) is a member of mammalian heme peroxidase family and is an enzyme of innate immune system. It possesses a covalently linked heme prosthetic group (a derivative of protoporphyrin IX) in its active site. LPO catalyzes the oxidation of halides and pseudohalides in the presence of hydrogen peroxide (H2O2) and shows a broad range of antimicrobial activity. Methods: In this study, we have used two pharmaceutically important drug molecules, namely dapsone and propofol, which are earlier reported as potent inhibitors of LPO. Whereas the stereochemistry and mode of binding of dapsone and propofol to LPO is still not known because of the lack of the crystal structure of LPO with these two drugs. In order to fill this gap, we utilized molecular docking and molecular dynamics (MD) simulation studies of LPO in native and complex forms with dapsone and propofol. Results: From the docking results, the estimated binding free energy (ΔG) of -9.25 kcal/mol (Ki = 0.16 μM) and -7.05 kcal/mol (Ki = 6.79 μM) was observed for dapsone, and propofol, respectively. The standard error of Auto Dock program is 2.5 kcal/mol; therefore, molecular docking results alone were inconclusive. Conclusion: To further validate the docking results, we performed MD simulation on unbound, and two drugs bounded LPO structures. Interestingly, MD simulations results explained that the structural stability of LPO-Propofol complex was higher than LPO-Dapsone complex. The results obtained from this study establish the mode of binding and interaction pattern of the dapsone and propofol to LPO as inhibitors.

Homology modeling and molecular docking studies of Drosophila and Aedes sex peptide receptors

2016 ◽  
Vol 66 ◽  
pp. 115-122 ◽  
Author(s):  
Jeong-hyun Kim ◽  
Soo-Kyung Kim ◽  
Jae-Hyuk Lee ◽  
Young-Joon Kim ◽  
William A. Goddard ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Homology Modeling ◽  
Docking Studies ◽  
Peptide Receptors ◽  
Molecular Docking Studies ◽  
Sex Peptide

Cellulase enzyme: Homology modeling, binding site identification and molecular docking

2017 ◽  
Vol 1150 ◽  
pp. 61-67 ◽  
Author(s):  
K. Selvam ◽  
D. Senbagam ◽  
T. Selvankumar ◽  
C. Sudhakar ◽  
S. Kamala-Kannan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Homology Modeling ◽  
Binding Site ◽  
Cellulase Enzyme ◽  
Binding Site Identification ◽  
Site Identification

scholarly journals Monoamine Neurotransmitters as Substrates for Novel Tick Sulfotransferases, Homology Modeling, Molecular Docking, and Enzyme Kinetics

2010 ◽  
Vol 6 (2) ◽  
pp. 176-184 ◽  
Author(s):  
Emine Bihter Yalcin ◽  
Hubert Stangl ◽  
Sivakamasundari Pichu ◽  
Thomas N. Mather ◽  
Roberta S. King
Keyword(s):  
Molecular Docking ◽  
Homology Modeling ◽  
Enzyme Kinetics ◽  
Monoamine Neurotransmitters

scholarly journals An Analysis Based on Molecular Docking and Molecular Dynamics Simulation Study of Bromelain as Anti-SARS-CoV-2 Variants

2021 ◽  
Vol 12 ◽  
Author(s):  
Trina Ekawati Tallei ◽  
Fatimawali ◽  
Afriza Yelnetty ◽  
Rinaldi Idroes ◽  
Diah Kusumawaty ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulation ◽  
Three Dimensional ◽  
Md Simulations ◽  
Inhibitory Effect ◽  
Dynamics Simulation ◽  
Novel Coronavirus

The rapid spread of a novel coronavirus known as SARS-CoV-2 has compelled the entire world to seek ways to weaken this virus, prevent its spread and also eliminate it. However, no drug has been approved to treat COVID-19. Furthermore, the receptor-binding domain (RBD) on this viral spike protein, as well as several other important parts of this virus, have recently undergone mutations, resulting in new virus variants. While no treatment is currently available, a naturally derived molecule with known antiviral properties could be used as a potential treatment. Bromelain is an enzyme found in the fruit and stem of pineapples. This substance has been shown to have a broad antiviral activity. In this article, we analyse the ability of bromelain to counteract various variants of the SARS-CoV-2 by targeting bromelain binding on the side of this viral interaction with human angiotensin-converting enzyme 2 (hACE2) using molecular docking and molecular dynamics simulation approaches. We have succeeded in making three-dimensional configurations of various RBD variants using protein modelling. Bromelain exhibited good binding affinity toward various variants of RBDs and binds right at the binding site between RBDs and hACE2. This result is also presented in the modelling between Bromelain, RBD, and hACE2. The molecular dynamics (MD) simulations study revealed significant stability of the bromelain and RBD proteins separately up to 100 ns with an RMSD value of 2 Å. Furthermore, despite increases in RMSD and changes in Rog values of complexes, which are likely due to some destabilized interactions between bromelain and RBD proteins, two proteins in each complex remained bonded, and the site where the two proteins bind remained unchanged. This finding indicated that bromelain could have an inhibitory effect on different SARS-CoV-2 variants, paving the way for a new SARS-CoV-2 inhibitor drug. However, more in vitro and in vivo research on this potential mechanism of action is required.

scholarly journals Homology Modeling and Structural Dynamics of the Glucose Oxidase

2019 ◽  
Vol 20 (1) ◽  
pp. 43
Author(s):  
Farhan Azhwin Maulana ◽  
Laksmi Ambarsari ◽  
Setyanto Tri Wahyudi
Keyword(s):  
Homology Modeling ◽  
Glucose Oxidase ◽  
Md Simulations ◽  
Data Bank ◽  
Positive Control ◽  
Glucose Biosensor ◽  
Amino Acid Sequences ◽  
Enzyme Thermostability ◽  
Modeled Structure ◽  
Reliable Model

Glucose oxidase from Aspergillus niger IPBCC.08.610 (GOD_IPBCC) is a locally sourced flavoenzyme from Indonesia that can potentially be developed in a variety of industrial processes. Although this enzyme has a high activity in catalyzing the redox reactions, the use of this enzyme was still limited to be applied as glucose biosensor. Using information from the amino acid sequences, a computational structure of GOD_IPBCC was therefore designed by homology modeling method using two homologous structures of GOD from protein data bank (1CF3 and 5NIT) as the templates. The quality of the resulting structures was evaluated geometrically for selection of the best model, and subsequently, 50 ns of MD simulations were carried out for the selected model as well as the corresponding template. Results obtained from the validation analysis showed that the 1CF3 template-built structure was selected as the best reliable model. The structural comparison exhibited that the best-modeled structure consisted of two functional domains and three catalytic residues similarly to the corresponding experimental structure. The overall dynamic behavior of the 50 ns of the structure was structurally stable and comparable with that of the positive control both from globally and locally observations. Implications of these stable nature within the best-modeled structure unfold the possibilities in search of notable residues and their roles to enhance enzyme thermostability.

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