scholarly journals Phosphatidylserine Exposed Lipid Bilayer Models for Understanding Cancer Cell Selectivity of Natural Compounds: A Molecular Dynamics Simulation Study

Membranes ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 64
Author(s):  
Navaneethan Radhakrishnan ◽  
Sunil C. Kaul ◽  
Renu Wadhwa ◽  
Durai Sundar
Keyword(s):  
Molecular Dynamics ◽  
Cell Membrane ◽  
Cancer Cells ◽  
Lipid Bilayers ◽  
Cancer Cell ◽  
Natural Compounds ◽  
Caffeic Acid Phenethyl Ester ◽  
Dynamics Simulation ◽  
Cell Selectivity ◽  
Dynamics Simulations

Development of drugs that are selectively toxic to cancer cells and safe to normal cells is crucial in cancer treatment. Evaluation of membrane permeability is a key metric for successful drug development. In this study, we have used in silico molecular models of lipid bilayers to explore the effect of phosphatidylserine (PS) exposure in cancer cells on membrane permeation of natural compounds Withaferin A (Wi-A), Withanone (Wi-N), Caffeic Acid Phenethyl Ester (CAPE) and Artepillin C (ARC). Molecular dynamics simulations were performed to compute permeability coefficients. The results indicated that the exposure of PS in cancer cell membranes facilitated the permeation of Wi-A, Wi-N and CAPE through a cancer cell membrane when compared to a normal cell membrane. In the case of ARC, PS exposure did not have a notable influence on its permeability coefficient. The presented data demonstrated the potential of PS exposure-based models for studying cancer cell selectivity of drugs.

scholarly journals A method for detection of permeation events in Molecular Dynamics simulations of lipid bilayers

2021 ◽  
Author(s):  
Carlos R. S. Camilo ◽  
J. Roberto Ruggiero ◽  
Alexandre S. de Araujo
Keyword(s):  
Molecular Dynamics ◽  
Cell Membrane ◽  
Lipid Bilayers ◽  
Complex Structure ◽  
Phospholipid Bilayer ◽  
Dynamics Simulation ◽  
Water Molecules ◽  
Human Knowledge ◽  
Crossing Time ◽  
Dynamics Simulations

The cell membrane is one of the most important structures of life. Understanding its functioning is essential for several human knowledge areas, mainly how it controls the efflux of substances between the cytoplasm and the environment. Being a complex structure, composed of several classes of compounds such as lipids, proteins, sugars, etc., a convenient way to mimic it is through a phospholipid bilayer. The Molecular Dynamics simulation of lipid bilayers in solution is the main computational approach to model the cell membrane. In this work, we present a method to detect permeation events of molecules through the lipid bilayer, characterizing its crossing time and trajectory. By splitting the simulation box into well-defined regions, the method distinguishes the passage of molecules through the bilayer from artifacts produced by crossing molecules through the simulation box edges when using periodic boundary conditions. We apply the method to study the spontaneous permeation of water molecules through bilayers with different lipid compositions and modeled with different force fields. Our method successfully characterizes the permeation events, and the results obtained show that the frequency and time of permeation are independent of the force field used to model the phospholipids. Besides, it is observed that the increase in the concentration of cholesterol molecules in lipid bilayers induces the reduction of permeation events due to its compacting action on the bilayer, making it denser and, therefore, hindering the diffusion of water molecules inside it. The computational tool to perform the method discussed here is available on https://github.com/crobertocamilo/MD-permeation.

scholarly journals Chloroform alters interleaflet coupling in lipid bilayers: an entropic mechanism

2015 ◽  
Vol 12 (106) ◽  
pp. 20150197 ◽  
Author(s):  
Ramon Reigada ◽  
Francesc Sagués
Keyword(s):  
Molecular Dynamics ◽  
Cell Membrane ◽  
Lipid Bilayers ◽  
Coarse Grained ◽  
General Anaesthetic ◽  
Computational Studies ◽  
Polar Compound ◽  
Cell Processes ◽  
Dynamics Simulations ◽  
Anaesthetic Action

The interaction of the two leaflets of the plasmatic cell membrane is conjectured to play an important role in many cell processes. Experimental and computational studies have investigated the mechanisms that modulate the interaction between the two membrane leaflets. Here, by means of coarse-grained molecular dynamics simulations, we show that the addition of a small and polar compound such as chloroform alters interleaflet coupling by promoting domain registration. This is interpreted in terms of an entropic gain that would favour frequent chloroform commuting between the two leaflets. The implication of this effect is discussed in relation to the general anaesthetic action.

pH-Dependent aggregation and pH-independent cell membrane adhesion of monolayer-protected mixed charged gold nanoparticles

Nanoscale ◽  
2019 ◽  
Vol 11 (15) ◽  
pp. 7371-7385 ◽  
Author(s):  
Zhiqiang Shen ◽  
William Baker ◽  
Huilin Ye ◽  
Ying Li
Keyword(s):  
Molecular Dynamics ◽  
Gold Nanoparticles ◽  
Cell Membrane ◽  
Molecular Dynamics Simulations ◽  
Lipid Bilayers ◽  
Coarse Grained ◽  
Ph Responsive ◽  
Ph Dependent ◽  
Membrane Adhesion ◽  
Dynamics Simulations

We systematically study the aggregation of pH-responsive AuNPs and their interactions with model lipid bilayers by using Martini coarse-grained molecular dynamics simulations.

Theoretical Study of the Process of Passage of Glycoside Amides through the Cell Membrane of Cancer Cell

2020 ◽  
Vol 20 ◽  
Author(s):  
Vasil Tsanov ◽  
Hristo Tsanov
Keyword(s):  
Cell Membrane ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Quantum Chemical ◽  
Density Functional ◽  
Enzyme Regulation ◽  
Amide Derivatives ◽  
Pass Through ◽  
Hydrolysis Of ◽  
Derivatives Of

Background:: This article concentrates on the processes occurring in the medium around the cancer cell and the transfer of glycoside amides through their cell membrane. They are obtained by modification of natural glycoside-nitriles (cyano-glycosides). Hydrolysis of starting materials in the blood medium and associated volume around physiologically active healthy and cancer cells, based on quantum-chemical semi-empirical methods, is considered. Objective:: Based on the fact that the cancer cell feeds primarily on carbohydrates, it is likely that organisms have adapted to take food containing nitrile glycosides and / or modified forms to counteract "external" bioactive activity. Cancers, for their part, have evolved to create conditions around their cells that eliminate their active apoptotic forms. This is far more appropriate for them than changing their entire enzyme regulation to counteract it. In this way, it protects itself and the gene sets and develops according to its instructions. Methods:: Derived pedestal that closely defines the processes of hydrolysis in the blood, the transfer of a specific molecular hydrolytic form to the cancer cell membrane and with the help of time-dependent density-functional quantum- chemical methods, its passage and the processes of re-hydrolysis within the cell itself, to forms causing chemical apoptosis of the cell - independent of its non-genetic set, which seeks to counteract the process. Results:: Used in oncology it could turn a cancer from a lethal to a chronic disease (such as diabetes). The causative agent and conditions for the development of the disease are not eliminated, but the amount of cancer cells could be kept low for a long time (even a lifetime). Conclusion:: The amide derivatives of nitrile glycosides exhibit anti-cancer activity, the cancer cell probably seeks to displace hydrolysis of these derivatives in a direction that would not pass through its cell membrane and the amide- carboxyl derivatives of nitrile glycosides could deliver extremely toxic compounds within the cancer cell itself and thus block and / or permanently damage its normal physiology.

Multicanonical Molecular Dynamics Simulation Study of the Liquid-Solid and Solid-Solid Transitions in Lennard-Jones Clusters

2011 ◽  
Author(s):  
Toshihiro Kaneko ◽  
Kenji Yasuoka ◽  
Ayori Mitsutake ◽  
Xiao Cheng Zeng
Keyword(s):  
Molecular Dynamics ◽  
Heat Capacity ◽  
Transition Temperature ◽  
Peak Position ◽  
Temperature Curve ◽  
Dynamics Simulation ◽  
Lennard Jones ◽  
Dynamics Simulations ◽  
First Time ◽  
Good Agreement

Multicanonical molecular dynamics simulations are applied, for the first time, to study the liquid-solid and solid-solid transitions in Lennard-Jones (LJ) clusters. The transition temperatures are estimated based on the peak position in the heat capacity versus temperature curve. For LJ31, LJ58 and LJ98, our results on the solid-solid transition temperature are in good agreement with previous ones. For LJ309, the predicted liquid-solid transition temperature is also in agreement with previous result.

scholarly journals Reactive molecular dynamics simulation of the high-temperature pyrolysis of 2,2′,2′′,4,4′,4′′,6,6′,6′′-nonanitro-1,1′:3′,1′′-terphenyl (NONA)

RSC Advances ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 5507-5515
Author(s):  
Liang Song ◽  
Feng-Qi Zhao ◽  
Si-Yu Xu ◽  
Xue-Hai Ju
Keyword(s):  
Molecular Dynamics ◽  
High Temperature ◽  
Molecular Dynamics Simulation ◽  
Molecular Dynamics Simulations ◽  
Dynamics Simulation ◽  
Reactive Molecular Dynamics ◽  
Ring Compounds ◽  
Fused Ring ◽  
Dynamics Simulations

The bimolecular and fused ring compounds are found in the high-temperature pyrolysis of NONA using ReaxFF molecular dynamics simulations.

scholarly journals Molecular dynamics simulations and experimental studies reveal differential permeability of withaferin-A and withanone across the model cell membrane

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Renu Wadhwa ◽  
Neetu Singh Yadav ◽  
Shashank P. Katiyar ◽  
Tomoko Yaguchi ◽  
Chohee Lee ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Cell Membrane ◽  
Molecular Dynamics Simulations ◽  
Experimental Studies ◽  
Bilayer Membrane ◽  
Withaferin A ◽  
Head Group ◽  
Polar Head Group ◽  
Natural Drugs ◽  
Dynamics Simulations

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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