Recognition of bio-relevant dicarboxylate anions by an azacalix[2]arene[2]triazine derivative decorated with urea moieties

2015 ◽  
Vol 13 (10) ◽  
pp. 3070-3085 ◽  
Author(s):  
Miguel M. Santos ◽  
Igor Marques ◽  
Sílvia Carvalho ◽  
Cristina Moiteiro ◽  
Vítor Félix
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Binding Affinity ◽  
H Nmr ◽  
Triazine Derivative ◽  
Wide Range ◽  
Dynamics Simulations ◽  
Nmr Titrations

The binding affinity of a dichlorocalix[2]arene[2]triazine based bis-urea azamacrocycle was investigated towards a wide range of bio-relevant dicarboxylate anions by a combination of 1H NMR titrations in CDCl3 and molecular dynamics simulations.

scholarly journals Identification of CDK7 Inhibitors from Natural Sources Using Pharmacoinformatics and Molecular Dynamics Simulations

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1197
Author(s):  
Vikas Kumar ◽  
Shraddha Parate ◽  
Gunjan Thakur ◽  
Gihwan Lee ◽  
Hyeon-Su Ro ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Binding Affinity ◽  
Cost Effective ◽  
Binding Mode ◽  
Kinase Domain ◽  
Dynamics Simulation ◽  
Mode Analysis ◽  
Atp Binding Site ◽  
Dynamics Simulations

The cyclin-dependent kinase 7 (CDK7) plays a crucial role in regulating the cell cycle and RNA polymerase-based transcription. Overexpression of this kinase is linked with various cancers in humans due to its dual involvement in cell development. Furthermore, emerging evidence has revealed that inhibiting CDK7 has anti-cancer effects, driving the development of novel and more cost-effective inhibitors with enhanced selectivity for CDK7 over other CDKs. In the present investigation, a pharmacophore-based approach was utilized to identify potential hit compounds against CDK7. The generated pharmacophore models were validated and used as 3D queries to screen 55,578 natural drug-like compounds. The obtained compounds were then subjected to molecular docking and molecular dynamics simulations to predict their binding mode with CDK7. The molecular dynamics simulation trajectories were subsequently used to calculate binding affinity, revealing four hits—ZINC20392430, SN00112175, SN00004718, and SN00262261—having a better binding affinity towards CDK7 than the reference inhibitors (CT7001 and THZ1). The binding mode analysis displayed hydrogen bond interactions with the hinge region residues Met94 and Glu95, DFG motif residue Asp155, ATP-binding site residues Thr96, Asp97, and Gln141, and quintessential residue outside the kinase domain, Cys312 of CDK7. The in silico selectivity of the hits was further checked by docking with CDK2, the close homolog structure of CDK7. Additionally, the detailed pharmacokinetic properties were predicted, revealing that our hits have better properties than established CDK7 inhibitors CT7001 and THZ1. Hence, we argue that proposed hits may be crucial against CDK7-related malignancies.

scholarly journals Peptide-Ligand Binding Modeling of siRNA with Cell-Penetrating Peptides

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Alfonso T. García-Sosa ◽  
Indrek Tulp ◽  
Kent Langel ◽  
Ülo Langel
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Binding Affinity ◽  
Cell Penetrating Peptides ◽  
Peptide Ligand ◽  
Intermolecular Hydrogen Bonds ◽  
Cell Penetrating ◽  
The Stability ◽  
Dynamics Simulations ◽  
Explicit Water

The binding affinity of a series of cell-penetrating peptides (CPP) was modeled through docking and making use of the number of intermolecular hydrogen bonds, lipophilic contacts, and the number of sp3 molecular orbital hybridization carbons. The new ranking of the peptides is consistent with the experimentally determined efficiency in the downregulation of luciferase activity, which includes the peptides’ ability to bind and deliver the siRNA into the cell. The predicted structures of the complexes of peptides to siRNA were stable throughout 10 ns long, explicit water molecular dynamics simulations. The stability and binding affinity of peptide-siRNA complexes was related to the sidechains and modifications of the CPPs, with the stearyl and quinoline groups improving affinity and stability. The reranking of the peptides docked to siRNA, together with explicit water molecular dynamics simulations, appears to be well suited to describe and predict the interaction of CPPs with siRNA.

Osmosis and Solute Size: A Molecular Dynamics Study

2011 ◽  
Author(s):  
James Cannon ◽  
Daejoong Kim ◽  
Shigeo Maruyama ◽  
Junichiro Shiomi
Keyword(s):  
Molecular Dynamics ◽  
Pressure Gradient ◽  
Molecular Dynamics Simulations ◽  
Osmotic Pressure ◽  
Essential Role ◽  
Osmotic Gradient ◽  
Wide Range ◽  
Dynamics Simulations ◽  
Osmotic Pressure Gradient

Osmosis plays an essential role in a wide range of phenomena, and therefore it is useful to understand how to manipulate the rate at which osmosis occurs. In the present study we conduct molecular dynamics simulations to consider the influence of solute size on the osmotic pressure gradient which drives the flow. Our results show how selective choice of the size of the solute can enhance, or hinder, the establishment of a strong osmotic gradient.

Thermal Conductivity of Polyethylene Chains Using Molecular Dynamics Simulations

2008 ◽  
Author(s):  
Asegun Henry ◽  
Gang Chen
Keyword(s):  
Thermal Conductivity ◽  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Polymer Chains ◽  
High Thermal Conductivity ◽  
Polymer Materials ◽  
Single Chain ◽  
Wide Range ◽  
Dynamics Simulations ◽  
Limiting Case

We used molecular dynamics simulations to calculate the thermal conductivity of polyethylene chains, by employing the widely used Green-Kubo formula. The simulations use the AIREBO potential and employ periodic boundary conditions to mimic the dynamics of an infinite chain. In this limiting case, we observed that when the simulation domain is large enough the thermal conductivity diverges. The results suggest that single polymer chains intrinsically have high thermal conductivity. Although polymers are generally known to have low thermal conductivity, our observation of divergent thermal conductivity in a single chain suggests that high thermal conductivity polymer materials can be engineered, which would be of interest to a wide range of applications.

Effect of interphase zone on the overall elastic properties of nanoparticle-reinforced polymer nanocomposites

2018 ◽  
Vol 53 (9) ◽  
pp. 1261-1274 ◽  
Author(s):  
Jafar Amraei ◽  
Jafar E Jam ◽  
Behrouz Arab ◽  
Roohollah D Firouz-Abadi
Keyword(s):  
Mechanical Properties ◽  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Polymer Nanocomposites ◽  
Volume Fraction ◽  
Finite Size ◽  
Radial Distance ◽  
Shear Moduli ◽  
Wide Range ◽  
Dynamics Simulations

In the current work, the effect of interphase region on the mechanical properties of polymer nanocomposites reinforced with nanoparticles is studied. For this purpose, a closed-form interphase model as a function of radial distance based on finite-size representative volume element is suggested to estimate the mechanical properties of particle-reinforced nanocomposites. The effective Young’s and shear moduli of thermoplastic polycarbonate-based nanocomposites for a wide range of sizes and volume fractions of silicon carbide nanoparticles are investigated using the proposed interphase model and molecular dynamics simulations. In order to investigate the effect of particle size, several unit cells of the same volume fraction, but with different particle radii have been considered. The micromechanics-based homogenization results are in good agreement with the results of molecular dynamics simulations for all models. This study demonstrates that the suggested micromechanical interphase model has the capacity to estimate effective mechanical properties of polymer-based nanocomposites reinforced with spherical inclusions.

Atomic Assembly of Thin Film Materials

2007 ◽  
Vol 539-543 ◽  
pp. 3528-3533
Author(s):  
X.W. Zhou ◽  
D.A. Murdick ◽  
B. Gillespie ◽  
J.J. Quan ◽  
Haydn N.G. Wadley ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Atomic Scale ◽  
Embedded Atom Method ◽  
Embedded Atom ◽  
Structures And Properties ◽  
Wide Range ◽  
Scale Structures ◽  
Kinetic Processes ◽  
Dynamics Simulations

The atomic-scale structures and properties of thin films are critically determined by the various kinetic processes activated during their atomic assembly. Molecular dynamics simulations of growth allow these kinetic processes to be realistically addressed at a timescale that is difficult to reach using ab initio calculations. The newest approaches have begun to enable the growth simulation to be applied for a wide range of materials. Embedded atom method potentials can be successfully used to simulate the growth of closely packed metal multilayers. Modified charge transfer ionic + embedded atom method potentials are transferable between metallic and ionic materials and have been used to simulate the growth of metal oxides on metals. New analytical bond order potentials are now enabling significantly improved molecular dynamics simulations of semiconductor growth. Selected simulations are used to demonstrate the insights that can be gained about growth processes at surfaces.

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