Molecular dynamics exploration of poration and leaking caused by Kalata B1 in HIV-infected cell membrane compared to host and HIV membranes

AbstractPoor bioavailability due to the inability to cross the cell membrane is one of the major reasons for the failure of a drug in clinical trials. We have used molecular dynamics simulations to predict the membrane permeability of natural drugs—withanolides (withaferin-A and withanone) that have similar structures but remarkably differ in their cytotoxicity. We found that whereas withaferin-A, could proficiently transverse through the model membrane, withanone showed weak permeability. The free energy profiles for the interaction of withanolides with the model bilayer membrane revealed that whereas the polar head group of the membrane caused high resistance for the passage of withanone, the interior of the membrane behaves similarly for both withanolides. The solvation analysis further revealed that the high solvation of terminal O5 oxygen of withaferin-A was the major driving force for its high permeability; it interacted with the phosphate group of the membrane that led to its smooth passage across the bilayer. The computational predictions were tested by raising and recruiting unique antibodies that react to withaferin-A and withanone. The time-lapsed analyses of control and treated cells demonstrated higher permeation of withaferin-A as compared to withanone. The concurrence between the computation and experimental results thus re-emphasised the use of computational methods for predicting permeability and hence bioavailability of natural drug compounds in the drug development process.

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Molecular Dynamics Simulations Provide Insight into the Loading Efficiency of Proresolving Lipid Mediators Resolvin D1 and D2 in Cell Membrane-Derived Nanovesicles

Molecular Pharmaceutics ◽

10.1021/acs.molpharmaceut.0c00299 ◽

2020 ◽

Vol 17 (6) ◽

pp. 2155-2164 ◽

Cited By ~ 1

Author(s):

Jeevan B. GC ◽

Christopher T. Szlenk ◽

Jin Gao ◽

Xinyue Dong ◽

Zhenjia Wang ◽

...

Keyword(s):

Molecular Dynamics ◽

Cell Membrane ◽

Molecular Dynamics Simulations ◽

Lipid Mediators ◽

Resolvin D1 ◽

Loading Efficiency ◽

Dynamics Simulations ◽

Insight Into

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Cellular Injection Using Carbon Nanotube: A Molecular Dynamics Study

NANO ◽

10.1142/s1793292015500253 ◽

2015 ◽

Vol 10 (02) ◽

pp. 1550025 ◽

Cited By ~ 4

Author(s):

Seyed Hanif Mahboobi ◽

Alireza Taheri ◽

Hossein Nejat Pishkenari ◽

Ali Meghdari ◽

Mahya Hemmat

Keyword(s):

Molecular Dynamics ◽

Carbon Nanotube ◽

Cell Membrane ◽

Minimally Invasive ◽

Lipid Bilayer ◽

Membrane Structure ◽

Md Simulations ◽

Injection Process ◽

Drug And Gene Delivery

Determination of an injection condition which is minimally invasive to the cell membrane is of great importance in drug and gene delivery. For this purpose, a series of molecular dynamics (MD) simulations are conducted to study the penetration of a carbon nanotube (CNT) into a pure POPC cell membrane under various injection velocities, CNT tilt angles and chirality parameters. The simulations are nonequilibrium and all-atom. The force and stress exerted on the nanotube, deformation of the lipid bilayer, and strain of the CNT atoms are inspected during the simulations. We found that a lower nanotube velocity results in successfully entering the membrane with minimum disruption in the CNT and the lipid bilayer, and CNT's chirality distinctly affects the results. Moreover, it is shown that the tilt angle of the CNT influences the nanotube's buckling and may result in destroying the membrane structure during the injection process.

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