scholarly journals Carbon Nanotubes Having Haeckelite Defects as Potential Drug Carriers. Molecular Dynamics Simulation

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4281
Author(s):  
Camila Torres ◽  
Ignacio Villarroel ◽  
Roberto Rozas ◽  
Leonor Contreras
Keyword(s):  
Carbon Nanotubes ◽  
Drug Delivery Systems ◽  
Nitrogen Doping ◽  
External Surface ◽  
Drug Carriers ◽  
Dynamics Simulation ◽  
Acidic Ph ◽  
Free Energies ◽  
Nanotube Chirality ◽  
Binding Free Energies

Carbon nanotubes (CNTs) are valuable drug carriers since when properly functionalized they transport drugs and anchor directly to cancerous tumors whose more acidic pH causes the drug release. Herein, we study the so-called zigzag and armchair CNTs with haeckelite defects to rank their ability to adsorb doxorubicin (DOX) by determining the DOX-CNT binding free energies using the MM/PBSA and MM/GBSA methods implemented in AMBER. Our results reveal stronger DOX-CNT interactions for encapsulation of the drug inside the nanotube compared to its adsorption onto the defective nanotube external surface. Armchair CNTs with one and two defects exhibit better results compared with those with four and fifteen defects. Each haeckelite defect consists of a pair of square and octagonal rings. DOX-CNT binding free energies are predicted to be dependent on: (i) nanotube chirality and diameter, (ii) the number of defects, (iii) nitrogen doping and (iv) the position of the encapsulated DOX inside the nanotube. Armchair (10,10) nanotubes with two haeckelite defects, doped with nitrogen, exhibit the best drug-nanotube binding free energies compared with zigzag and fully hydrogenated nanotubes and, also previously reported ones with bumpy defects. These results contribute to further understanding drug-nanotube interactions and their potential application to the design of new drug delivery systems.

scholarly journals Doxorubicin Encapsulation in Carbon Nanotubes Having Haeckelite or Stone–Wales Defects as Drug Carriers: A Molecular Dynamics Approach

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1586
Author(s):  
Leonor Contreras ◽  
Ignacio Villarroel ◽  
Camila Torres ◽  
Roberto Rozas
Keyword(s):  
Carbon Nanotubes ◽  
Molecular Dynamics ◽  
Drug Delivery Systems ◽  
Nitrogen Doping ◽  
Drug Carriers ◽  
Acidic Ph ◽  
Free Energies ◽  
Interaction Forces ◽  
Chiral Nanotubes ◽  
Binding Free Energies

Doxorubicin (DOX), a recognized anticancer drug, forms stable associations with carbon nanotubes (CNTs). CNTs when properly functionalized have the ability to anchor directly in cancerous tumors where the release of the drug occurs thanks to the tumor slightly acidic pH. Herein, we study the armchair and zigzag CNTs with Stone–Wales (SW) defects to rank their ability to encapsulate DOX by determining the DOX-CNT binding free energies using the MM/PBSA and MM/GBSA methods implemented in AMBER16. We investigate also the chiral CNTs with haeckelite defects. Each haeckelite defect consists of a pair of square and octagonal rings. The armchair and zigzag CNT with SW defects and chiral nanotubes with haeckelite defects predict DOX-CNT interactions that depend on the length of the nanotube, the number of present defects and nitrogen doping. Chiral nanotubes having two haeckelite defects reveal a clear dependence on the nitrogen content with DOX-CNT interaction forces decreasing in the order 0N > 4N > 8N. These results contribute to a further understanding of drug-nanotube interactions and to the design of new drug delivery systems based on CNTs.

Investigations on the mechanisms of interactions between matrix metalloproteinase 9 and its flavonoid inhibitors using a combination of molecular docking, hybrid quantum mechanical/molecular mechanical calculations, and molecular dynamics simulations

2014 ◽  
Vol 92 (9) ◽  
pp. 821-830 ◽  
Author(s):  
Zhi-Guang Zhou ◽  
Qi-Zheng Yao ◽  
Dong Lei ◽  
Qing-Qing Zhang ◽  
Ji Zhang
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulations ◽  
Biological Activities ◽  
Dynamics Simulation ◽  
Quantum Mechanical ◽  
Free Energies ◽  
Hydrogen Bond Networks ◽  
Dynamics Simulations ◽  
Binding Free Energies

Many experimental studies have found that flavonoids can inhibit the activities of matrix metalloproteinases (MMPs), but the relevant mechanisms are still unclear. In this paper, the interaction mechanisms of MMP-9 with its five flavonoid inhibitors are investigated using a combination of molecular docking, hybrid quantum mechanical and molecular mechanical (QM/MM) calculations, and molecular dynamics simulations. The molecular dynamics simulation results show a good linear correlation between the calculated binding free energies of QM/MM−Poisson–Boltzmann surface area (PBSA) and the experimental −log(EC50) regarding the studied five flavonoids on MMP-9 inhibition in explicit solvent. It is found that compared with the MM−PBSA method, the QM/MM−PBSA method can obviously improve the accuracy for the calculated binding free energies. The predicted binding modes of the five flavonoid−MMP-9 complexes reveal that the different hydrogen bond networks can form besides producing the Zn−O coordination bonds, which can reasonably explain previous experimental results. The agreement between our calculated results and the previous experimental facts indicates that the force field parameters used here are effective and reliable for investigating the systems of flavonoid−MMP-9 interactions, and thus, these simulations and analyses could be reproduced for the other related systems involving protein−ligand interactions. This paper may be helpful for designing the new MMP-9 inhibitors having higher biological activities by carrying out the structural modifications of flavonoid molecules.

scholarly journals Atomic Structure and Energy Distribution of Collapsed Carbon Nanotubes of Different Chiralities

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Julia A. Baimova ◽  
Qin Fan ◽  
Liangcai Zeng ◽  
Zhigang Wang ◽  
Sergey V. Dmitriev ◽  
...  
Keyword(s):  
Carbon Nanotubes ◽  
Molecular Dynamics ◽  
Distribution Function ◽  
Molecular Dynamics Simulation ◽  
Low Temperature ◽  
Energy Distribution ◽  
Ground State ◽  
Large Diameter ◽  
Dynamics Simulation ◽  
Nanotube Chirality

For carbon nanotubes of sufficiently large diameter at sufficiently low temperature, due to the action of the van der Waals forces, the ground state is a bilayer graphene with closed edges, the so-called collapsed configuration. Molecular dynamics simulation of collapsed carbon nanotubes is performed. The effect of length, diameter, and chirality of the nanotubes on their properties is investigated. It is shown that collapsed nanotubes after relaxation have rippled structure which is strongly dependent on the nanotube chirality. The structural properties are studied by calculating the radial distribution function and energy distribution along various regions in the collapsed carbon nanotubes.

scholarly journals Discovery of Novel Inhibitors Targeting HDM2: Virtual Screening, Molecular Dynamics Simulation and Binding affinity predication

2021 ◽  
Author(s):  
Feng Cao ◽  
Liang Chen ◽  
Feng Xiong ◽  
Xingyong Liu ◽  
Li Zhang
Keyword(s):  
Molecular Dynamics ◽  
Virtual Screening ◽  
Drug Target ◽  
Dynamics Simulation ◽  
Free Energies ◽  
Tumor Treatment ◽  
Mechanism Of Interaction ◽  
Insight Into ◽  
Important Drug ◽  
Binding Free Energies

Abstract HDM2(human double-minute 2 protein) is an important drug target for tumor treatment. The main physiological function of HDM2 is to negatively regulate the tumor suppressor protein p53 and inhibit the normal biological function of p53, which leads to the occurrence and development of tumors. Therefore, the discovery of small molecules that can inhibit the activity of HDM2 is a promising cancer therapy. In this study, we reported a virtual screening as an effective strategy to discover potential HDM2 inhibitors from the Specs database. Then 100 ns all-atom molecular dynamics (MD) simulation and binding free energies calculated were carried out on the selected compounds. In conclusion, we reported seven prospective candidates with novel skeletons among them Hit4 is a potential HDM2 inhibitor and provided an insight into the mechanism of interaction of the compounds to HDM2 target.

Synthesis, characterization and molecular dynamics simulation of the polyacrylates membranes

e-Polymers ◽  
2016 ◽  
Vol 16 (1) ◽  
pp. 83-89 ◽  
Author(s):  
Xiaoping Zhan ◽  
Yuxuan Xin ◽  
Kai Zhao ◽  
Shuai Wang ◽  
Jian Chen ◽  
...  
Keyword(s):  
Drug Delivery Systems ◽  
Drug Carriers ◽  
Permeation Rate ◽  
Polymer Chains ◽  
Polymer Materials ◽  
Dynamics Simulation ◽  
Fractional Free Volume ◽  
Drug Molecules ◽  
Transdermal Drug Delivery Systems ◽  
Simulation Results

AbstractThe aims of this paper are to investigate the inherent relationship between the structures of the polyacrylates and release behaviors as drug carriers in the transdermal drug delivery systems. Three model polyacrylates compounds were synthesized by radical polymerization. Three polymer materials were characterized by Fourier transform infrared, differential scanning calorimeter and cytotoxicity, and the release behaviors of drug molecules transporting through the polymers membranes were tested. Moreover, the effects of the polymers’ structures on the permeability were studied by molecular dynamic simulation. The simulation results showed that higher chains mobility and larger fractional free volume of the polymer membranes resulted in higher permeation rates. By comparing the monomers’ structure in the polymer materials, it was found that the polymer chains’ mobility decreases, and permeation rate correspondingly decreases with the increase in the amount and volume of side groups on the double bonds.

scholarly journals A molecular dynamics simulation study of interactions between aprotinin and transmembrane serine proteases TMPRSS2 and prostasin

2020 ◽  
Author(s):  
C Solis-Calero ◽  
HF Carvalho
Keyword(s):  
Hydrogen Bond ◽  
Free Energy ◽  
Serine Protease ◽  
Free Energy Calculations ◽  
Dynamics Simulation ◽  
Free Energies ◽  
Hydrogen Bond Networks ◽  
Free Energy Decomposition ◽  
Transmembrane Serine Protease ◽  
Binding Free Energies

Aprotinin is a small protein, which inhibits trypsin and related proteolytic enzymes, it has been shown experimentally that it can inhibit SARS-CoV-2 replication.However, the molecular mechanisms relate to it are not totally known. TMPRSS2 is a human transmembrane serine protease which is important for viral spread and pathogenesis. In the current study, we use homology modeling for obtaining an initial structure of the complex between aprotinin and TMPRSS2, having as template the crystallographic structure of the complex between aprotinin and prostasin, other transmembrane serine protease which is related to other processes such as the regulation of hypertension. The binding modes of both complexes were predicted based on initial geometry optimization, and molecular dynamic simulations, calculating MM/PBSA and MM/GBSA free-energy calculations after the simulations. The calculated binding free energies suggested a better affinity of TMPRSS2 to aprotinin than prostasin. Moreover, hydrogen bond analyses along the trajectory simulation showed that the hydrogen-bond networks between TMPRSS2 and aprotinin are more stable than the corresponding to prostasin and aprotinin which explain their higher binding free energies. Additionally, in order to elucidate the different contributions of KLK14 residues to the free energy of binding, MM/GBSA free-energy decomposition analyses were performed. Based on their results, Glu97, Glu144H, Asp189 and Ser190 residues have been postulated as TMPRSS2 potential hotspots for its binding to aprotinin and by extension to other possible inhibitors.

Evaluating the Covalent Binding of Carbapenems on BlaC Using Noncovalent Interactions

2021 ◽  
Author(s):  
Lu Sun ◽  
Hongjun Fan ◽  
Shijun Zhong
Keyword(s):  
Noncovalent Interactions ◽  
Binding Free Energy ◽  
Covalent Binding ◽  
Tight Binding ◽  
Covalent Bonding ◽  
Noncovalent Interaction ◽  
Free Energy Calculations ◽  
Dynamics Simulation ◽  
Free Energies ◽  
Binding Free Energies

Abstract Carbapenems, as irreversible covalent binders and slow substrates to the Class A β-lactamase (BlaC) of Mycobacterium tuberculosis, can inhibit BlaC to hydrolyze the β-lactam drugs which are used to control tuberculosis. Their binding on BlaC involves covalent bonding and noncovalent interaction. We introduce a hypothesis that the noncovalent interactions dominate the difference of binding free energies for covalent ligands based on the assumption that their covalent bonding energies are same. MM/GBSA binding free energies calculated from the noncovalent interactions, provided a threshold with respect to the experimental kinetic data, to select slow carbapenem substrates which were either constructed using the structural units of experimentally identified carbapenems or obtained from the similarity search over the ZINC15 database. Combining molecular docking with consensus scoring and molecular dynamics simulation with MM/GBSA binding free energy calculations, a computational protocol was developed from which several new tight-binding carbapenems were theoretically identified.

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