scholarly journals Trends in the Binding of Cell Penetrating Peptides to siRNA: A Molecular Docking Study

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
P. V. G. M. Rathnayake ◽  
B. G. C. M. Gunathunge ◽  
P. N. Wimalasiri ◽  
D. N. Karunaratne ◽  
R. J. K. U. Ranatunga
Keyword(s):  
Molecular Docking ◽  
Electrostatic Interactions ◽  
Hydrophobic Interactions ◽  
Docking Study ◽  
Cell Penetrating Peptides ◽  
Molecular Docking Study ◽  
Hydrophobic Peptides ◽  
Cell Penetrating ◽  
Docking Calculations ◽  
Cellular Import

The use of gene therapeutics, including short interfering RNA (siRNA), is limited by the lack of efficient delivery systems. An appealing approach to deliver gene therapeutics involves noncovalent complexation with cell penetrating peptides (CPPs) which are able to penetrate the cell membranes of mammals. Although a number of CPPs have been discovered, our understanding of their complexation and translocation of siRNA is as yet insufficient. Here, we report on computational studies comparing the binding affinities of CPPs with siRNA, considering a variety of CPPs. Specifically, seventeen CPPs from three different categories, cationic, amphipathic, and hydrophobic CPPs, were studied. Molecular mechanics were used to minimize structures, while molecular docking calculations were used to predict the orientation and favorability of sequentially binding multiple peptides to siRNA. Binding scores from docking calculations were highest for amphipathic peptides over cationic and hydrophobic peptides. Results indicate that initial complexation of peptides will likely occur along the major groove of the siRNA, driven by electrostatic interactions. Subsequent binding of CPPs is likely to occur in the minor groove and later on bind randomly, to siRNA or previously bound CPPs, through hydrophobic interactions. However, hydrophobic CPPs do not show this binding pattern. Ultimately binding yields a positively charged nanoparticle capable of noninvasive cellular import of therapeutic molecules.

scholarly journals A Dispersion Corrected DFT Investigation of the Inclusion Complexation of Dexamethasone with β-Cyclodextrin and Molecular Docking Study of Its Potential Activity against COVID-19

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7622
Author(s):  
Youghourta Belhocine ◽  
Seyfeddine Rahali ◽  
Hamza Allal ◽  
Ibtissem Meriem Assaba ◽  
Monira Galal Ghoniem ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Active Sites ◽  
Density Functional ◽  
Inclusion Complexation ◽  
Docking Study ◽  
Van Der Waals Interactions ◽  
Molecular Docking Study ◽  
Main Protease ◽  
Docking Calculations ◽  
Potential Activity

The encapsulation mode of dexamethasone (Dex) into the cavity of β-cyclodextrin (β-CD), as well as its potential as an inhibitor of the COVID-19 main protease, were investigated using density functional theory with the recent dispersion corrections D4 and molecular docking calculations. Independent gradient model and natural bond orbital approaches allowed for the characterization of the host–guest interactions in the studied systems. Structural and energetic computation results revealed that hydrogen bonds and van der Waals interactions played significant roles in the stabilization of the formed Dex@β-CD complex. The complexation energy significantly decreased from −179.50 kJ/mol in the gas phase to −74.14 kJ/mol in the aqueous phase. A molecular docking study was performed to investigate the inhibitory activity of dexamethasone against the COVID-19 target protein (PDB ID: 6LU7). The dexamethasone showed potential therapeutic activity as a SARS CoV-2 main protease inhibitor due to its strong binding to the active sites of the protein target, with predicted free energy of binding values of −29.97 and −32.19 kJ/mol as calculated from AutoDock4 and AutoDock Vina, respectively. This study was intended to explore the potential use of the Dex@β-CD complex in drug delivery to enhance dexamethasone dissolution, thus improving its bioavailability and reducing its side effects.

scholarly journals In Silico Study on N-Ferrocenylmethyl-N-Phenylpropionohydrazide and N-Ferrocenylmethyl-N-Pheylbenzohydrazide as Anticancer Drugs for Breast and Prostate Cancer

2018 ◽  
Vol 11 ◽  
pp. 17-25 ◽  
Author(s):  
Zegheb Nadjiba ◽  
Boubekri Chérifa ◽  
Touhami Lanez ◽  
Elhafnaoui Lanez
Keyword(s):  
Prostate Cancer ◽  
Free Energy ◽  
Molecular Docking ◽  
Hydrogen Bonds ◽  
Binding Free Energy ◽  
Docking Study ◽  
Dominant Mode ◽  
Molecular Docking Study ◽  
Docking Calculations ◽  
Breast And Prostate Cancer

Molecular docking calculations were used to evaluate the antitumor activities of N-ferrocenylmethyl-N-phenylpropanamide (FP) and N-ferrocenylmethyl-N-pheylbenzohydrazide (FH) against the enzymes of breast cancer 17-beta-hydroxysteroid dehydrogenase type 1 (17β-HSD1) and human steroidogenic cytochrome P450 17A1 prostate cancer mutant A105L (CYP17A1). The molecular docking study was performed using the open source AutoDock 4.2 software. The obtained results showed that both FP and FH bind with 17β-HSD1 and CYP17A1 via hydrogen bonds, binding free energy values for the adducts FH-17β-HSD1 and FH-CYP17A1 were respectively equal to-27.67 and-27.55 KJmol-1, while for the adducts FP-17β-HSD1 and FP-CYP17A1 they were respectively equal to-29.13 and 29.18 KJmol-1. The negative values and the magnitude of the obtained binding free energy indicated respectively the spontaneity and the electrostatic interaction of both ligands FP and FH with 17β-HSD1 and CYP17A1 receptors as the dominant mode. Finally the ligand FP binds more strongly to the receptor CYP17A1 and forms two respective hydrogen bonds with Arg96 and His373; this finding clearly indicate that FP is best qualified as potential drug candidature for breast and prostate cancer.

Novel Guanosine Derivatives as Anti-HCV NS5b Polymerase: A QSAR and Molecular Docking Study

2019 ◽  
Vol 15 (2) ◽  
pp. 130-137 ◽  
Author(s):  
Abdo A. Elfiky
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Active Site ◽  
Docking Study ◽  
Binding Affinities ◽  
Molecular Docking Study ◽  
Docking Calculations ◽  
Quantitative Structure Activity Relationships ◽  
Hcv Ns5b ◽  
Ns5b Polymerase

Background: IDX-184 is a guanosine derivative having a potent inhibitory performance against HCV NS5b polymerase. Objective: To test three different groups of 2'C - modified analogues of guanosine nucleotide against HCV polymerase. Method: Using combined Quantitative Structure-Activity Relationships (QSAR) and molecular docking, the suggested compounds are studied. Results: Examining the docked structures of the compounds with experimentally solved NS5b structure (PDB ID: 2XI3) revealed that most of the compounds have the same mode of interaction as that of guanosine nucleotide and hence, NS5b inhibition is possible. Conclusion: It is revealed that sixteen modifications have a better binding affinity to NS5b compared to guanosine. In addition, seven more compounds are better in NS5b binding compared to the approved drug, sofosbuvir, and the compound under clinical trials, IDX-184. Hence, these compounds could be potent HCV NS5b inhibitors. Summary Points: Novel guanosine modifications were introduced in silico and optimized using QM. QSAR and docking calculations are performed to test the binding affinity of the compounds to HCV NS5b active site. Comparison between the binding affinities and the mode of interactions of the compounds and both GTP and IDX-184 is performed. Structural mining to quantify the mode of binding of the compounds to NS5b active site pocket.

scholarly journals DOCKING STUDIES IN TARGET PROTEINS INVOLVED IN ANTIBACTERIAL ACTION MECHANISMS: ALKALOIDS ISOLATED FROM SCUTELLARIA GENUS

2016 ◽  
Vol 9 (5) ◽  
pp. 121 ◽  
Author(s):  
Sri Dharani R ◽  
Ranjitha R ◽  
Sripathi R ◽  
Ali Muhammad K S ◽  
Ravi S
Keyword(s):  
Cell Wall ◽  
Molecular Docking ◽  
Hydrophobic Interactions ◽  
Docking Study ◽  
Docking Studies ◽  
Cell Wall Synthesis ◽  
Molecular Docking Study ◽  
Bacterial Proteins ◽  
Antimicrobial Studies ◽  
Action Mechanisms

ABSTRACTObjective: In the present work, docking study was performed for 22 selected alkaloids isolated from the genus Scutellaria to evaluate their affinityto bacterial proteins that are known targets for many antibiotics with a different mechanism of action: Inhibitors of cell wall synthesis, inhibitors ofnucleic acids synthesis and antimetabolites.Methods: Molecular docking study was carried out using AutoDock 4.2 version and the visualization result using Chimera 1.10 and DiscoveryStudio 4.5.Result: Among the 22 alkaloids studied, with the DNA gyrase protein 1KZN and a dihydropteroate synthase enzyme 3TYE, the compoundscutebarbatine E showed a docking score of −8.5 and −8.7 Kcal/mol, respectively, involving with hydrophilic and hydrophobic interactions. Withrespect to MurD ligase involved in cell wall synthesis 1UAG and 2X5O, the compound 6,7,nicotinyl scutebarbatine G fared well with a dockingscore of −10.1 and −10.2 Kcal/mol, respectively. Scutebarbatine G performed well with respect to 3UDI with binding scores of −9.3 K cal/mol.Conclusion: Overall, it seems that for the selected alkaloids from the genus Scutellaria, the main mechanism of the action is the inhibition of cell wallsynthesis.Keywords: Scutebarbatine, Alkaloids, Molecular docking, Antimicrobial studies.

EVALUATION OF IN-SILICO ANTICANCER POTENTIAL OF PYRETHROIDS: A COMPARATIVE MOLECULAR DOCKING STUDY

2015 ◽  
Author(s):  
Manik Ghosh ◽  
Kamal Kant ◽  
Anoop Kumar ◽  
Padma Behera ◽  
Naresh Rangra ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Study ◽  
Molecular Docking Study

Myricetin Preferentially Binds to Interfacial Regions in Domains 1 – 3 to Inhibit Cholesterol-Dependent Cytolysins: A Molecular Docking Study

2020 ◽  
Author(s):  
Rafael Espiritu
Keyword(s):  
Molecular Docking ◽  
Structural Changes ◽  
Docking Study ◽  
Listeriolysin O ◽  
Molecular Docking Study ◽  
Docking Analysis ◽  
Streptolysin O ◽  
Molecule Inhibitor ◽  
Human Cd59 ◽  
Anthrolysin O

<p>Cholesterol-dependent cytolysins (CDCs) are proteinaceous toxins secreted as monomers by some Gram-positive and Gram-negative bacteria that contribute to their pathogenicity. These toxins bind to either cholesterol or human CD59, leading to massive structural changes, toxin oligomerization, formation of very large pores, and ultimately cell death, making these proteins promising targets for inhibition. Myricetin, and its related flavonoids, have been previously identified as a candidate small molecule inhibitor of specific CDCs such as listeriolysin O (LLO) and suilysin (SLY), interfering with their oligomerization. In this work, molecular docking was performed to assess the interaction of myricetin with other CDCs whose crystal structures are already known. Results indicated that although myricetin bound to the hitherto identified cavity in domain 4 (D4), much more efficient and stable binding was obtained in sites along the interfacial regions of domains 1 – 3 (D1 – D3). This was common among the tested CDCs, which was primarily due to much more extensive stabilizing intermolecular interactions, as indicated by post-docking analysis. Specifically, myricetin bound to (1) the interface of the three domains in anthrolysin O (ALO), perfringolysin O (PFO), pneumolysin (PLY), SLY, and vaginolysin (VLY), (2) at/near the D1/D3 interface in LLO and streptolysin O (SLO), and (3) along the D2/D3 interface in intermedilysin (ILY). These findings provide theoretical basis on the possibility of using myricetin and its related compounds as a broad-spectrum inhibitor of CDCs to potentially address the diseases associated with these pathogens.</p>

Computational Evidences of Phytochemical Mediated Disruption of PLpro Driven Replication of SARS-CoV-2: A Therapeutic Approach Against COVID-19

2020 ◽  
Vol 21 ◽  
Author(s):  
Acharya Balkrishna ◽  
Rashmi Mittal ◽  
Vedpriya Arya
Keyword(s):  
Molecular Docking ◽  
Md Simulation ◽  
Bond Distance ◽  
Immunological Response ◽  
Docking Study ◽  
Receptor Interaction ◽  
Molecular Docking Study ◽  
Replication Process ◽  
Stable Conformation ◽  
Distance Analysis

Background:: COVID-19 caused by SARS-CoV-2 has been declared as global pandemic by WHO. Comprehensive analysis of this unprecedented outbreak may help to fight against the disease and may play a pivotal role in decreasing the mortality rate linked with it. Papain like protease (PLpro), a multifunctional polyprotein facilitates the replication of SARS-CoV-2 and evades it from the host immunological response by antagonizing cytokines, interferons and may be considered as potential drug target to combat the current pandemic. Methods:: Natural moieties obtained from medicinal plants were analysed for their potency to target PLpro of SARS-CoV-2 by molecular docking study and were compared with synthetic analogs named as remdesivir, chloroquine and favipiravir. The stability of complexes of top hits was analysed by MD Simulation and interaction energy was calculated. Furthermore, average RMSD values were computed and deepsite ligand binding pockets were predicted using Play Molecule. Drug like abilities of these moieties were determined using ADMET and bond distance between the ligand and active site was assessed to predict the strength of interaction. Results:: Nimbocinol (-7.6 Kcal/mol) and sage (-7.3 Kcal/mol) exhibited maximum BA against PLpro SARS-CoV-2 as evident from molecular docking study which was found to be even better than remdesivir (-6.1 Kcal/mol), chloroquine (-5.3 Kcal/mol) and favipiravir (-5.7 Kcal/mol). Both nimbocinol-PLpro and sage-PLpro SARS-CoV-2 complex exhibited stable conformation during MD Simulation of 101ns at 310 K and potential, kinetic and electrostatic interaction energies were computed which was observed to be concordant with results of molecular docking study. RMSD average values were found to be 0.496 ± 0.015 Å and 0.598 ± 0.023 Å for nimbocinol and sage respectively thus revealing that both the deviation and fluctuations during MD Simulation were observed to be least. Deepsite prediction disclosed that both compounds occupied cryptic pockets in receptor and non-bond distance analysis revealed the formation of hydrogen bonds during ligand-receptor interaction. ADMET exploration further validated the drug like properties of these compounds. Conclusion:: Present study revealed that active constituents of Azadirachta indica and Salvia officinalis can be potentially used to target SARS-CoV-2 by hindering its replication process.

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