SPECIFIC BINDING OF A SHORT miRNA SEQUENCE BY ZINC KNUCKLES OF Lin28: A MOLECULAR DYNAMICS SIMULATION STUDY

2013 ◽  
Vol 12 (08) ◽  
pp. 1341015
Author(s):  
CHENG TAN ◽  
WENFEI LI ◽  
WEI WANG
Keyword(s):  
Molecular Dynamics ◽  
Binding Affinity ◽  
Conformational Changes ◽  
Rna Binding ◽  
Specific Binding ◽  
Md Simulations ◽  
Dynamics Simulation ◽  
Mirna Sequence ◽  
Physiological Importance ◽  
Terminal Loop

Protein Lin28 recognizes pre-let-7 microRNAs (miRNAs) through direct interactions between its zinc-knuckle type zinc-finger (ZnF) domains and the terminal loop of pre-let-7, resulting in the inhibition of the synthesis of mature let-7 miRNAs. Despite the physiological importance, the involved conformational changes and energetic factors contributing to the binding affinity and specificity remain unclear. We conducted molecular dynamics (MD) simulations in conjunction with molecular mechanics/generalized born surface area (MM/GBSA) and energy decomposition calculations to investigate the RNA binding-induced conformational changes of the ZnFs and the residual level energetic factors that influence the binding affinity and specificity. We showed that the binding of the RNA results in the inter-domain conformational changes of the two ZnF domains, including changes of the spatial relationships of several nucleobase-binding amino acids. We also observed mutation-induced weakening of the affinity of the Lin28–pre-let-7 binding, which reveals the importance of the stacking interactions between the side-chains of Tyr140, His148, His162 and the bases of nucleic acid G2 and G5 in the specific recognition of pre-let-7 by the ZnFs of Lin28.

A MOLECULAR DYNAMICS SIMULATION STUDY OF CONFORMATIONAL CHANGES AND SOLVATION OF Aβ PEPTIDE IN TRIFLUOROETHANOL AND WATER

2009 ◽  
Vol 08 (02) ◽  
pp. 215-231 ◽  
Author(s):  
S. JALILI ◽  
M. AKHAVAN
Keyword(s):  
Molecular Dynamics ◽  
Secondary Structure ◽  
Conformational Changes ◽  
Pure Water ◽  
Sodium Dodecyl ◽  
Md Simulations ◽  
Dynamics Simulation ◽  
Amyloid Beta Peptide ◽  
Sodium Dodecyl Sulfate Micelle ◽  
Beta Peptide

Molecular dynamics (MD) simulations of amyloid beta peptide have been performed in aqueous solutions of trifluoroethanol with different concentrations. The amount of α-helical secondary structure increases when going from pure water to trifluoroethanol-rich solutions. The conformation obtained in 40% (v/v) trifluoroethanol solution is very similar to the experimental observations of beta peptide in sodium dodecyl sulfate micelle. In this solution, the peptide has two helical segments connected through a looped region. The C-terminal helix of beta peptide unfolds in pure water. The effect of trifluoroethanol on peptide's secondary structure has been explained using the properties calculated from MD trajectories.

scholarly journals Understanding Covalent Grafting of Nanotubes onto Polymer Nanocomposites: Molecular Dynamics Simulation Study

Sensors ◽  
2021 ◽  
Vol 21 (8) ◽  
pp. 2621
Author(s):  
Seunghwa Yang
Keyword(s):  
Molecular Dynamics ◽  
Load Transfer ◽  
Cell Model ◽  
Md Simulations ◽  
Dynamics Simulation ◽  
Covalent Grafting ◽  
Modelling Strategies ◽  
Multi Walled Carbon Nanotubes ◽  
Walled Carbon Nanotubes ◽  
External Loads

Here, we systematically interrogate the effects of grafting single-walled (SWNT) and multi-walled carbon nanotubes (MWNT) to polymer matrices by using molecular dynamics (MD) simulations. We specifically investigate key material properties that include interfacial load transfer, alteration of nanotube properties, and dispersion of nanotubes in the polymer matrix. Simulations are conducted on a periodic unit cell model of the nanocomposite with a straight carbon nanotube and an amorphous polyethylene terephthalate (PET) matrix. For each type of nanotube, either 0%, 1.55%, or 3.1% of the carbon atoms in the outermost nanotubes are covalently grafted onto the carbon atoms of the PET matrix. Stress-strain curves and the elastic moduli of nanotubes and nanocomposites are determined based on the density of covalent grafting. Covalent grafting promotes two rivalling effects with respect to altering nanotube properties, and improvements in interfacial load transfer in the nanocomposites are clearly observed. The enhanced interface enables external loads applied to the nanocomposites to be efficiently transferred to the grafted nanotubes. Covalent functionalization of the nanotube surface with PET molecules can alter the solubility of nanotubes and improve dispersibility. Finally, we discuss the current limitations and challenges in using molecular modelling strategies to accurately predict properties on the nanotube and polymers systems studied here.

scholarly journals Molecular Docking and Molecular Dynamics Simulation Studies of Triterpenes from Vernonia patula with the Cannabinoid Type 1 Receptor

2021 ◽  
Vol 22 (7) ◽  
pp. 3595
Author(s):  
Md Afjalus Afjalus Siraj ◽  
Md. Sajjadur Rahman ◽  
Ghee T. Tan ◽  
Veronique Seidel
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulation ◽  
Binding Affinity ◽  
Docking Studies ◽  
Dynamics Simulation ◽  
Simulation Studies ◽  
Cannabinoid Type 1 Receptor ◽  
Docking Approach

A molecular docking approach was employed to evaluate the binding affinity of six triterpenes, namely epifriedelanol, friedelin, α-amyrin, α-amyrin acetate, β-amyrin acetate, and bauerenyl acetate, towards the cannabinoid type 1 receptor (CB1). Molecular docking studies showed that friedelin, α-amyrin, and epifriedelanol had the strongest binding affinity towards CB1. Molecular dynamics simulation studies revealed that friedelin and α-amyrin engaged in stable non-bonding interactions by binding to a pocket close to the active site on the surface of the CB1 target protein. The studied triterpenes showed a good capacity to penetrate the blood–brain barrier. These results help to provide some evidence to justify, at least in part, the previously reported antinociceptive and sedative properties of Vernonia patula.

A Study on the Uniaxial Tension of FCC Metals at Nano Level Using MD

2008 ◽  
Vol 32 ◽  
pp. 255-258
Author(s):  
Bohayra Mortazavi ◽  
Akbar Afaghi Khatibi
Keyword(s):  
Molecular Dynamics ◽  
Uniaxial Tension ◽  
Md Simulations ◽  
Dynamics Simulation ◽  
Face Centered Cubic ◽  
Engineering Strain ◽  
Fcc Metals ◽  
Engineering Stress ◽  
Nano Science ◽  
Face Centered

Molecular Dynamics (MD) are now having orthodox means for simulation of matter in nano-scale. It can be regarded as an accurate alternative for experimental work in nano-science. In this paper, Molecular Dynamics simulation of uniaxial tension of some face centered cubic (FCC) metals (namely Au, Ag, Cu and Ni) at nano-level have been carried out. Sutton-Chen potential functions and velocity Verlet formulation of Noise-Hoover dynamic as well as periodic boundary conditions were applied. MD simulations at different loading rates and temperatures were conducted, and it was concluded that by increasing the temperature, maximum engineering stress decreases while engineering strain at failure is increasing. On the other hand, by increasing the loading rate both maximum engineering stress and strain at failure are increasing.

Molecular Dynamics Simulation of a Pullout Test on a Carbon Nanotube in a Polymer Matrix

2014 ◽  
Vol 1700 ◽  
pp. 61-66
Author(s):  
Guttormur Arnar Ingvason ◽  
Virginie Rollin
Keyword(s):  
Molecular Dynamics ◽  
Polymer Matrix ◽  
Large Scale ◽  
Md Simulations ◽  
Dynamics Simulation ◽  
Atomistic Simulations ◽  
Polymer Molecules ◽  
Molecular Potential ◽  
Pull Out ◽  
Walled Carbon Nanotubes

ABSTRACTAdding single walled carbon nanotubes (SWCNT) to a polymer matrix can improve the delamination properties of the composite. Due to the complexity of polymer molecules and the curing process, few 3-D Molecular Dynamics (MD) simulations of a polymer-SWCNT composite have been run. Our model runs on the Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS), with a COMPASS (Condensed phase Optimized Molecular Potential for Atomistic Simulations Studies) potential. This potential includes non-bonded interactions, as well as bonds, angles and dihedrals to create a MD model for a SWCNT and EPON 862/DETDA (Diethyltoluenediamine) polymer matrix. Two simulations were performed in order to test the implementation of the COMPASS parameters. The first one was a tensile test on a SWCNT, leading to a Young’s modulus of 1.4 TPa at 300K. The second one was a pull-out test of a SWCNT from an originally uncured EPON 862/DETDA matrix.

THE "FOLDING" BEHAVIORS OF HOMOPOLYMERS WITH ONE END FIXED

2004 ◽  
Vol 18 (15) ◽  
pp. 2123-2139 ◽  
Author(s):  
BIN XUE ◽  
JUN WANG ◽  
WEI WANG
Keyword(s):  
Molecular Dynamics ◽  
Chain Length ◽  
Conformational Changes ◽  
Canonical Ensemble ◽  
Interaction Strength ◽  
Simulation Method ◽  
Dynamics Simulation ◽  
Radius Of Gyration ◽  
Native Conformation ◽  
Collapse Temperature

We study the "folding" behaviors of homopolymers with one end fixed. By using canonical ensemble molecular dynamics simulation method, we observe the conformational changes during folding processes. Long chains collapse to the helical nuclei, then regroup to helix from the free-end to form the compact conformations through the middle stages of helix-like coil and helix-like cone, while short chains do not apparently have the above mentioned middle stages. Through simulated annealing, the native conformation of homopolymer chain in our model is found to be helix. We show the relations between specific heat C v (T) and radius of gyration R g (T) as functions of temperature, chain length and the interaction strength, respectively. We find that these two quantities match well and can be combined to interpret the "folding" process of the homopolymer. It is found that the collapse temperature Tθ and the native-like folding temperature T f do not change with the chain length in our model, however the interaction strength affects the values of Tθ and T f .

scholarly journals Polypharmacology of Some Medicinal Plant Metabolites Against SARS-CoV-2 and Host Targets: Molecular Dynamics Evaluation of NSP9 RNA Binding Protein

2020 ◽  
Author(s):  
Suritra Bandyopadhyay ◽  
Omobolanle Abimbola Abiodun ◽  
Blessing Chinweotito Ogboo ◽  
Adeola Tawakalitu Kola-Mustapha ◽  
Emmanuel Ifeanyi Attah ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Medicinal Plants ◽  
Active Sites ◽  
Rna Binding ◽  
Hydrophobic Interactions ◽  
Binding Energies ◽  
Dynamics Simulation ◽  
Receptor Interaction ◽  
Plant Metabolites ◽  
Structure Comparison

<p><b>Background: </b>Medicinal plants, as rich sources of bioactive compounds with antiviral properties, are now being explored for the development of drugs against SARS-CoV-2.</p><p><b>Aims: </b>Identification of promising compounds for the treatment of COVID-19 from natural products via molecular modelling against NSP9, including some other viral and host targets and evaluation of polypharmacological indications.</p><p><b>Main methods: </b>A manually curated library of 521 phytochemicals (from 19 medicinal plants) was virtually screened using Mcule server and binding interactions were studied using DS Visualiser. Docking thresholds were set based on the scores of standard controls and rigorous ADMET properties were used to finally get the potential inhibitors. Free binding energies of the docked complexes were calculated employing MM-GBSA method. MM-GBSA informed our choice for MD simulation studies performed against NSP9 to study the stability of the drug-receptor interaction. NSP9 structure comparison was also performed. </p><p><b>Key findings: </b>Extensive screening of the molecules identified 5 leads for NSP9, 23 for Furin, 18 for ORF3a, and 19 for interleukin-6. Ochnaflavone and Licoflavone B, obtained from Lonicera japonica (Japanese Honeysuckle) and Glycyrrhiza glabra (Licorice), respectively, were identified to have the highest potential multi-target inhibition properties for NSP9, furin, ORF3a, and IL-6. Additionally, molecular dynamics simulation supports the robust stability of Ochnaflavone and Licoflavone B against NSP9 at the active sites via hydrophobic interactions, H-bonding, and H-bonding facilitated by water.</p><b>Significance:</b> These compounds with the highest drug-like ranking against multiple viral and host targets have the potential to be drug candidates for the treatment of SARS-CoV-2 infection that may possibly act on multiple pathways simultaneously to inhibit viral entry and replication as well as disease progression.

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.

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