scholarly journals Scrutiny of the mechanism of β-amyloid protein captures HSV-2 to protect the brain infection

2021 ◽  
Vol 261 ◽  
pp. 02069
Author(s):  
Qiuxian Zhang ◽  
Hecheng Wang
Keyword(s):  
Molecular Dynamics ◽  
Neurodegenerative Disorder ◽  
Binding Free Energy ◽  
Experimental Studies ◽  
Dynamics Simulation ◽  
Amyloid Protein ◽  
Brain Infection ◽  
Age Related ◽  
Β Amyloid ◽  
Dynamics Simulations

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder. β-amyloid protein (Aβ) is the key protein which involved in AD. But the physiological function of Aβ is needed to be investigated. Many experimental studies have shown that Aβ could bind to glycoproteins D (gD) on the surface of the herpes virus. However the mechanism is still unclear. In the present study, we elucidate the molecular mechanism of the interaction between Aβ and gD of herpes simplex virus type 2 (HSV-2) by molecular docking and molecular dynamics simulation. Molecular dynamics simulations displayed that Aβ could stably bind to the HSV-2 gD owing to the presence of several interactions. Analysis binding free energy by molecular mechanics Poisson–Boltzmann surface area (MM–PBSA) method revealed that hot residues including Glu3, Glu11, Glu22 and Ala42 of Aβ1-42 were involved in binding with HSV-2 gD. Thus, the HSV-2 gD can be entrapped by Aβ which will be utilized for prevent and therapy of AD in future.

MOLECULAR MODELING OF THE INTERACTIONS BETWEEN HISTONE DEACETYLASE 8 AND INHIBITORS

2012 ◽  
Vol 11 (04) ◽  
pp. 907-924 ◽  
Author(s):  
DAWEI HUANG ◽  
XIAOHUI LI ◽  
ZHILONG XIU
Keyword(s):  
Molecular Dynamics ◽  
Histone Deacetylases ◽  
Hydrophobic Interactions ◽  
Binding Free Energy ◽  
Zinc Ion ◽  
Dynamics Simulation ◽  
Amino Acid Residues ◽  
Domain Docking ◽  
Dynamics Simulations ◽  
Linker Domain

Inhibitors of histone deacetylases (HDACs) have become an attractive class of anticancer agent. To understand the interaction between HDAC8 and inhibitors, including "pan-" inhibitors that inhibit many HDACs isoforms and selective inhibitors with no linker domain, docking and molecular dynamics simulation were conducted. Docking results showed the presence of π-π interactions between "linkerless" inhibitors and the aromatic amino acid residues of HDAC8 in the active site. Binding between HDAC8 and inhibitors was also stabilized by hydrogen bond and hydrophobic interaction. In molecular dynamics simulations, the zinc ion was shown to coordinate one more atom of HDAC8-"linkerless" inhibitor complexes than HDAC8-"pan-" inhibitor complexes. Persistent hydrogen bonds also existed between Tyr306 of HDAC8 and some inhibitors. When inhibitors with large cap groups bound to the active pocket of HDAC8, Phe152 and Met274 shifted from their initial positions and the entrance of the active pocket became more open, resulting in the formation of sub-pocket. Hydrophobic interactions contributed most favorably to the binding free energy between HDAC8 and inhibitors. Lys33, Asp178, Asp267, Tyr306 and Leu308 of HDAC8 were favorable for binding with all inhibitors.

scholarly journals Identification of Potential Binders of the SARS-Cov-2 Spike Protein via Molecular Docking, Dynamics Simulation and Binding Free Energy Calculation

2020 ◽  
Author(s):  
Dr. Chirag N. Patel ◽  
Dr. Prasanth Kumar S. ◽  
Dr. Himanshu A. Pandya ◽  
Dr. Rakesh M. Rawal
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Molecular Docking ◽  
Molecular Dynamics Simulations ◽  
Binding Free Energy ◽  
Free Energy Calculations ◽  
Dynamics Simulation ◽  
Spike Protein ◽  
Energy Calculations ◽  
Dynamics Simulations

<p>The pandemic outbreak of COVID-19 virus (SARS-CoV-2) has become critical global health issue. The biophysical and structural evidence shows that SARS-CoV-2 spike protein possesses higher binding affinity towards angiotensin-converting enzyme 2 (ACE2) and hemagglutinin-acetylesterase (HE) glycoprotein receptor. Hence, it was selected as a target to generate the potential candidates for the inhibition of HE glycoprotein. The present study focuses on extensive computational approaches which contains molecular docking, ADMET prediction followed by molecular dynamics simulations and free energy calculations. Furthermore, virtual screening of NPACT compounds identified 3,4,5-Trihydroxy-1,8-bis[(2R,3R)-3,5,7-trihydroxy-3,4-dihydro-2H-chromen-2-yl]benzo[7]annulen-6-one, Silymarin, Withanolide D, Spirosolane and Oridonin were interact with high affinity. The ADMET prediction revealed pharmacokinetics and drug-likeness properties of top-ranked compounds. Molecular dynamics simulations and binding free energy calculations affirmed that these five NPACT compounds were robust HE inhibitor.</p>

Drug resistance mechanisms of three mutations V32I, I47V and V82I in HIV-1 protease toward inhibitors probed by molecular dynamics simulations and binding free energy predictions

RSC Advances ◽  
2016 ◽  
Vol 6 (63) ◽  
pp. 58573-58585 ◽  
Author(s):  
Jianzhong Chen
Keyword(s):  
Molecular Dynamics ◽  
Drug Resistance ◽  
Free Energy ◽  
Binding Free Energy ◽  
Resistance Mechanisms ◽  
Free Energy Calculations ◽  
Dynamics Simulation ◽  
Probe Drug ◽  
Dynamics Simulations ◽  
Hiv 1

Molecular dynamics simulation and binding free energy calculations were used to probe drug resistance of HIV-1 protease mutations toward inhibitors.

scholarly journals Molecular Dynamics Simulations of Acetylcholinesterase – Beta-Amyloid Peptide Complex

2020 ◽  
Vol 20 (6) ◽  
pp. 140-154
Author(s):  
Mariana Atanasova ◽  
Ivan Dimitrov ◽  
Stefan Ivanov
Keyword(s):  
Molecular Dynamics ◽  
Neurodegenerative Disorder ◽  
Beta Amyloid ◽  
Amyloid Peptide ◽  
Dynamics Simulation ◽  
Aβ Peptide ◽  
Ache Inhibitors ◽  
Aβ Aggregation ◽  
The Stability ◽  
Dynamics Simulations

AbstractAlzheimer’s Disease (AD) is a neurodegenerative disorder with severe consequences and lethal outcome. One of the pathological hallmarks of the disease is the formation of insoluble intercellular beta-Amyloid (Aβ) plaques. The enzyme ACetylcholinEsterase (AChE) promotes and accelerates the aggregation of toxic Aβ protofibrils progressively converted into plaques. The Peripheral Anionic Site (PAS), part of the binding gorge of AChE, is one of the nucleation centers implicated in the Aβ aggregation. In this study, the Aβ peptide was docked into the PAS and the stability of the formed complex was investigated by molecular dynamics simulation for 1 μs (1000 ns). The complex was stable during the simulation. Apart from PAS, the Aβ peptide makes several additional contacts with AChE. The main residence area of Aβ on the surface of AChE is the region 344-361. This region is next to PAS but far enough to be sterically hindered by dual-site binding AChE inhibitors.

scholarly journals Identification of Potential Binders of the SARS-Cov-2 Spike Protein via Molecular Docking, Dynamics Simulation and Binding Free Energy Calculation

2020 ◽  
Author(s):  
Dr. Chirag N. Patel ◽  
Dr. Prasanth Kumar S. ◽  
Dr. Himanshu A. Pandya ◽  
Dr. Rakesh M. Rawal
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Molecular Docking ◽  
Molecular Dynamics Simulations ◽  
Binding Free Energy ◽  
Free Energy Calculations ◽  
Dynamics Simulation ◽  
Spike Protein ◽  
Energy Calculations ◽  
Dynamics Simulations

<p>The pandemic outbreak of COVID-19 virus (SARS-CoV-2) has become critical global health issue. The biophysical and structural evidence shows that SARS-CoV-2 spike protein possesses higher binding affinity towards angiotensin-converting enzyme 2 (ACE2) and hemagglutinin-acetylesterase (HE) glycoprotein receptor. Hence, it was selected as a target to generate the potential candidates for the inhibition of HE glycoprotein. The present study focuses on extensive computational approaches which contains molecular docking, ADMET prediction followed by molecular dynamics simulations and free energy calculations. Furthermore, virtual screening of NPACT compounds identified 3,4,5-Trihydroxy-1,8-bis[(2R,3R)-3,5,7-trihydroxy-3,4-dihydro-2H-chromen-2-yl]benzo[7]annulen-6-one, Silymarin, Withanolide D, Spirosolane and Oridonin were interact with high affinity. The ADMET prediction revealed pharmacokinetics and drug-likeness properties of top-ranked compounds. Molecular dynamics simulations and binding free energy calculations affirmed that these five NPACT compounds were robust HE inhibitor.</p>

Molecular dynamics simulation and free energy analysis of the interaction of platinum-based anti-cancer drugs with DNA

2016 ◽  
Vol 15 (06) ◽  
pp. 1650054 ◽  
Author(s):  
Seifollah Jalili ◽  
Mina Maddah ◽  
Jeremy Schofield
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Hydrogen Bonds ◽  
Binding Free Energy ◽  
Double Helix ◽  
Free Energy Calculations ◽  
Dynamics Simulation ◽  
Cancer Drugs ◽  
Anti Cancer ◽  
Dynamics Simulations

Cisplatin and oxaliplatin are two widely-used anti-cancer drugs which covalently bind to a same location in DNA strands. Platinum agents make intrastrand and interstrand cross-links with the N7 atoms of guanine nucleotides which prevent DNA from polymerization by causing a distortion in the double helix. Molecular dynamics simulations and free energy calculations were carried out to investigate the binding of two platinum-based anti-cancer drugs with DNA. We compared the binding of these drugs which differ in their carrier ligands, and hence their potential interactions with DNA. When a platinum agent binds to nucleotides, it causes a high amount of deformation in DNA structure. To find the extent of deformation, torsion angles and base pair and groove parameters of DNA were considered. These parameters were compared with normal B-DNA which was considered as the undamaged DNA. The formation of hydrogen bonds between drugs and DNA nucleotides was examined in solution. It was shown that oxaliplatin forms more hydrogen bonds than cisplatin. Our results confirm that the structure of the platinated DNA rearranges significantly and cisplatin tries to deform DNA more than oxaliplatin. The binding free energies were also investigated to understand the affinities, types and the contributions of interactions between drugs and DNA. It was concluded that oxaliplatin tendency for binding to DNA is more than cisplatin in solvent environment. The binding free energy was calculated based on the MM/PBSA and MM/GBSA methods and the results of QM/MM calculations verified them.

scholarly journals Molecular docking and dynamics simulations reveal the potential of anti-HCV drugs to inhibit COVID-19 main protease

2021 ◽  
Author(s):  
Ahmed Ali Al-Karmalawy ◽  
Radwan Alnajjar ◽  
Mohammed Dahab ◽  
Ahmed Metwaly ◽  
Ibrahim Eissa
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Binding Free Energy ◽  
Solvent Accessibility ◽  
Genetic Material ◽  
New Drugs ◽  
Dynamics Simulation ◽  
Main Protease ◽  
Natural Inhibitor ◽  
Dynamics Simulations

Background: Drug repurposing is the fastest effective method to provide treatment for coronavirus disease (COVID-19). Drugs that targeting a closely related virus with similar genetic material such as hepatitis C virus (HCV) and more specifically targeting a similar viral protease would be an excellent choice. Methods: In this study, we carried out a virtual screening for fifteen anti HCV drugs against COVID-19 main protease using computational molecular docking techniques. Moreover, Velpatasvir (4) and Sofosbuvir (13) drugs were further evaluated through molecular dynamics simulations followed by calculating the binding free energy using the molecular mechanics generalised born/solvent accessibility (MM-GBSA) approach. Results: The binding affinity descending order was N3 natural inhibitor (1), Velpatasvir (4), Sofosbuvir (13), Ombitasvir (3), Glecaprevir (2), Asunaprevir (8), Paritaprevir (10), Grazoprevir (11), Elbasvir (6), Ledipasvir (5), Daclatasvir (7), Pibrentasvir (9), Simeprevir (12), Dasabuvir (14), Taribavirin (16) and finally Ribavirin (15). Molecular dynamics simulation reveals that Sofosbuvir (13) has exciting properties and it was stable within the active site; it also showed good MM-GBSA compared to the natural inhibitor N3. Conclusion: Our results could be auspicious for fast repurposing of the examined drugs either alone or in combinations with each other for the treatment of the COVID-19. Furthermore, this work provides a clear spot on the structure-activity relationship (SAR) for targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease and helps the design and synthesis of new drugs in the future targeting it as well.

scholarly journals A Comparative Study of Binding of Different Drugs on gp120: Insight from Molecular Dynamics Simulation Study

2018 ◽  
Vol 34 (6) ◽  
pp. 2954-2962
Author(s):  
Vishnudatt Pandey ◽  
Gargi Tiwari ◽  
Rajendra Prasad Ojha
Keyword(s):  
Molecular Dynamics ◽  
Protein Interactions ◽  
Binding Sites ◽  
Binding Free Energy ◽  
Dynamics Simulation ◽  
Receptor Protein ◽  
Contact Points ◽  
Gp120 Binding ◽  
Cd4 Binding Site ◽  
Dynamics Simulations

HIV-I cellular infection triggered by CD4 receptor protein and viral envelop glycoprotein gp120 binding event. CD4:gp120 surface is directed by the contact points of a hydrophobic gp120 cavity capped by Phe43CD4 and ionic bonds residues Arg59CD4 and Asp368gp120. The binding sites originated by gp120 and CD4 interaction leads to the entry of HIV-I into the host membrane, where, gp120 and a CD4 binding site becomes the main mark for plenty of drug uncovering program. Here, we took the crystal structure of small-molecule of gp120 in a complex that concurrently pursues both of the hotspots of gp120 binding sites. All ligands in our study are small molecules that are able to obstruct the protein-protein interactions between CD4 and gp120. This study aims at the thermodynamical insights of the ligand binding in CD4 binding sites using Molecular Dynamics Simulations Study and calculation of binding free energy. The physical of binding of drugs distinctly indicates a hydrophobic and electrostatics interaction motivated binding of ligands which explicitly mark CD4 binding sites.

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