scholarly journals Exploring the Binding Pattern of Geraniol with Acetylcholinesterase through In Silico Docking, Molecular Dynamics Simulation, and In Vitro Enzyme Inhibition Kinetics Studies

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3533
Author(s):  
Danish Iqbal ◽  
M. Salman Khan ◽  
Mohd Waiz ◽  
Md Tabish Rehman ◽  
Mohammed Alaidarous ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Enzyme Inhibition ◽  
In Silico ◽  
Neuromuscular Disorders ◽  
Dynamics Simulation ◽  
Inhibition Kinetics ◽  
Stable Conformation ◽  
Enzyme Inhibition Kinetics

Acetylcholinesterase (AChE) inhibition is a key element in enhancing cholinergic transmission and subsequently relieving major symptoms of several neurological and neuromuscular disorders. Here, the inhibitory potential of geraniol and its mechanism of inhibition against AChE were elucidated in vitro and validated via an in silico study. Our in vitro enzyme inhibition kinetics results show that at increasing concentrations of geraniol and substrate, Vmax did not change significantly, but Km increased, which indicates that geraniol is a competitive inhibitor against AChE with an IC50 value 98.06 ± 3.92 µM. All the parameters of the ADME study revealed that geraniol is an acceptable drug candidate. A docking study showed that the binding energy of geraniol (−5.6 kcal mol−1) was lower than that of acetylcholine (−4.1 kcal mol−1) with AChE, which exhibited around a 12.58-fold higher binding affinity of geraniol. Furthermore, molecular dynamics simulation revealed that the RMSD of AChE alone or in complex with geraniol fluctuated within acceptable limits throughout the simulation. The mean RMSF value of the complex ensures that the overall conformation of the protein remains conserved. The average values of Rg, MolSA, SASA, and PSA of the complex were 3.16 Å, 204.78, 9.13, and 51.58 Å2, respectively. We found that the total SSE of AChE in the complex was 38.84% (α-helix: 26.57% and β-sheets: 12.27%) and remained consistent throughout the simulation. These findings suggest that geraniol remained inside the binding cavity of AChE in a stable conformation. Further in vivo investigation is required to fully characterize the pharmacokinetic properties, optimization of dose administration, and efficacy of this plant-based natural compound.

Exploring the Molecular Mechanisms of 17β-HSD5-induced Carcinogenicity of Catha Edulis via Molecular Modeling Approach.

2020 ◽  
Vol 16 ◽  
Author(s):  
Maria Saeed ◽  
Sajda Ashraf ◽  
Rashad Alsanosi ◽  
Hassan A. Alhazmi ◽  
Mohammed AlBratty ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
In Silico ◽  
Molecular Mechanisms ◽  
Dynamics Simulation ◽  
Catha Edulis ◽  
Khat Chewing ◽  
First Time

Background: The tradition of khat chewing has been deep-rooted in the African and Arabian Peninsula for centuries. Due to its amphetamine-like psycho-stimulant or euphoric effect, Khat has been used by millions in Somalia, Ethiopia, Saudi Arabia and Yemen. The long-term use of Khat can induce tremendous health outcomes, which may be serious and irreversible. Objective: Prolong use of Khat constituents has been associated with different types of cancers such as prostatic, breast and ovarian cancer. However, it has been very difficult to identify the molecular targets involved in Khat carcinogenesis that interact with the Khat constituents by in vitro/in vivo experimental tools. Method: In silico tools to predict potential targets involved in the carcinogenesis of Khat. Pass on-line prediction server was used for the prediction of a potential molecular target for Khat constituents. Molecular Dynamics simulation and MMGBSA calculation of the predicted target. Results: Molecular Dynamics simulation and MM-GBSA calculation. Results revealed that among Khat constituents βSitosterol showed high binding affinity towards 17β-HSD5. On the other hand, this study highlights for the first time, some new interactions, which were observed in the case of cathine, cathinone and nerol during the simulation. Conclusion: In silico molecular dynamic simulation tools were used for the first time to investigate the molecular mechanism of widely used leaves of psychoactive Khat (Catha edulis) constituent, which is used extensively all over the world. The present study provides deep insight to understand the effect of Khat constituents involve in the impairment of reproductive system and its binding to 17β-HSD5. ADMET profiling also suggested that few Khat constituents do not fulfill the requirements of Lipinski rule of five i.e. poor absorption and blood-brain barrier impermeability.

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.

Longan seed polyphenols inhibit α-amylase activity and reduce postprandial glycemic response in mice

2021 ◽  
Author(s):  
Ting He ◽  
lei zhao ◽  
Yan Chen ◽  
Xin Zhang ◽  
Zhuoyan Hu ◽  
...  
Keyword(s):  
Enzyme Inhibition ◽  
Amylase Activity ◽  
Glycemic Response ◽  
Inhibition Assay ◽  
Inhibition Kinetics ◽  
Enzyme Inhibition Kinetics ◽  
Longan Seed ◽  
Kinetics Of

The effects of longan seed polyphenols (LSPs) on postprandial glycemic response in mice were investigated, enzyme inhibition kinetics of LSPs against α-amylase were studied using an inhibition assay in vitro,...

In vitro evaluation and molecular dynamics, DFT guided investigation of antimalarial activity of ethnomedicinally used Coptis teeta Wall

2021 ◽  
Vol 24 ◽  
Author(s):  
Ashis Kumar Goswami ◽  
Hemanta Kumar Sharma ◽  
Neelutpal Gogoi ◽  
Ankita Kashyap ◽  
Bhaskar Jyoti Gogoi
Keyword(s):  
Molecular Dynamics ◽  
In Silico ◽  
Density Functional ◽  
Antimalarial Activity ◽  
In Silico Analysis ◽  
Dynamics Simulation ◽  
Discovery Studio ◽  
North East ◽  
Silico Analysis

Background: Malaria is caused by different species of Plasmodium; among which P. falciparum is the most severe. Coptis teeta is an ethnomedicinal plant of enormous importance for tribes of north east India. Objective: In this study, the anti malarial activity of the methanol extracts of Coptis teeta was evaluated in vitro and lead identification via in silico study. Method: On the basis of the in vitro results, in silico analysis by application of different modules of Discovery Studio 2018 was performed on multiple targets of P. falciparum taking into consideration some of the compounds reported from C. teeta. Results: The IC50 of the methanol extract of Coptis teeta 0.08 µg/ml in 3D7 strain and 0.7 µg/ml in Dd2 strain of P. falciparum. From the docking study, noroxyhydrastatine was observed to have better binding affinity in comparison to chloroquine. The binding of noroxyhydrastinine with dihydroorotate dehydrogenase was further validated by molecular dynamics simulation and was observed to be significantly stable in comparison to the co-crystal inhibitor. During simulations it was observed that noroxyhydrastinine retained the interactions, giving strong indications of its effectiveness against the P. falciparum proteins and stability in the binding pocket. From the Density-functional theory analysis, the band gap energy of noroxyhydrastinine was found to be 0.186 Ha indicating a favourable interaction. Conclusion: The in silico analysis as an addition to the in vitro results provide strong evidence of noroxyhydrastinine as an anti malarial agent.

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