Distribution of neutral prilocaine in a phospholipid bilayer: Insights from molecular dynamics simulations

2008 ◽  
Vol 108 (13) ◽  
pp. 2386-2391 ◽  
Author(s):  
Mónica Pickholz ◽  
Leonardo Fernandes Fraceto ◽  
Eneida de Paula
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Phospholipid Bilayer ◽  
Dynamics Simulations

scholarly journals Anionic nanoparticle-induced perturbation to phospholipid membranes affects ion channel function

2020 ◽  
Vol 117 (45) ◽  
pp. 27854-27861
Author(s):  
Isabel U. Foreman-Ortiz ◽  
Dongyue Liang ◽  
Elizabeth D. Laudadio ◽  
Jorge D. Calderin ◽  
Meng Wu ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Molecular Dynamics ◽  
Ion Channel ◽  
Molecular Dynamics Simulations ◽  
Lipid Bilayers ◽  
Phospholipid Bilayer ◽  
Biophysical Properties ◽  
Channel Function ◽  
Dynamics Simulations ◽  
Membrane Mechanical Properties

Understanding the mechanisms of nanoparticle interaction with cell membranes is essential for designing materials for applications such as bioimaging and drug delivery, as well as for assessing engineered nanomaterial safety. Much attention has focused on nanoparticles that bind strongly to biological membranes or induce membrane damage, leading to adverse impacts on cells. More subtle effects on membrane function mediated via changes in biophysical properties of the phospholipid bilayer have received little study. Here, we combine electrophysiology measurements, infrared spectroscopy, and molecular dynamics simulations to obtain insight into a mode of nanoparticle-mediated modulation of membrane protein function that was previously only hinted at in prior work. Electrophysiology measurements on gramicidin A (gA) ion channels embedded in planar suspended lipid bilayers demonstrate that anionic gold nanoparticles (AuNPs) reduce channel activity and extend channel lifetimes without disrupting membrane integrity, in a manner consistent with changes in membrane mechanical properties. Vibrational spectroscopy indicates that AuNP interaction with the bilayer does not perturb the conformation of membrane-embedded gA. Molecular dynamics simulations reinforce the experimental findings, showing that anionic AuNPs do not directly interact with embedded gA channels but perturb the local properties of lipid bilayers. Our results are most consistent with a mechanism in which anionic AuNPs disrupt ion channel function in an indirect manner by altering the mechanical properties of the surrounding bilayer. Alteration of membrane mechanical properties represents a potentially important mechanism by which nanoparticles induce biological effects, as the function of many embedded membrane proteins depends on phospholipid bilayer biophysical properties.

scholarly journals Molecular Dynamics Simulations of Mitochondrial Uncoupling Protein 2

2021 ◽  
Vol 22 (3) ◽  
pp. 1214
Author(s):  
Sanja Škulj ◽  
Zlatko Brkljača ◽  
Jürgen Kreiter ◽  
Elena E. Pohl ◽  
Mario Vazdar
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Proton Transport ◽  
Uncoupling Protein ◽  
Homology Modelling ◽  
Md Simulations ◽  
Phospholipid Bilayer ◽  
Mitochondrial Membranes ◽  
Fatty Acid Binding ◽  
Dynamics Simulations

Molecular dynamics (MD) simulations of uncoupling proteins (UCP), a class of transmembrane proteins relevant for proton transport across inner mitochondrial membranes, represent a complicated task due to the lack of available structural data. In this work, we use a combination of homology modelling and subsequent microsecond molecular dynamics simulations of UCP2 in the DOPC phospholipid bilayer, starting from the structure of the mitochondrial ATP/ADP carrier (ANT) as a template. We show that this protocol leads to a structure that is impermeable to water, in contrast to MD simulations of UCP2 structures based on the experimental NMR structure. We also show that ATP binding in the UCP2 cavity is tight in the homology modelled structure of UCP2 in agreement with experimental observations. Finally, we corroborate our results with conductance measurements in model membranes, which further suggest that the UCP2 structure modeled from ANT protein possesses additional key functional elements, such as a fatty acid-binding site at the R60 region of the protein, directly related to the proton transport mechanism across inner mitochondrial membranes.

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