Molecular Dynamics Study of Cytochrome C – Lipid Complexes

Trusova, Valeriya; Gorbenko, Galyna; Tarabara, Uliana; Vus, Kateryna; Ryzhova, Olga

doi:10.26565/2312-4334-2017-3-08

Cited by 4 publications

(1 citation statement)

References 55 publications

(57 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During the last decades the molecular dynamics simulation has become a powerful tool in characterizing the atomic-level details of the interaction between peptides [25,26], proteins [27], organic solvents [28,29] and drugs [30] with lipid membranes. Moreover, MD simulation appeared to be especially useful in studying the behavior of fluorescent membrane probes [31][32][33][34].…”

Section: Resultsmentioning

confidence: 99%

Molecular Dynamics Simulation of the Interaction Between Benzanthrone Dye and Model Lipid Membranes

Zhytniakivska

2020

EEJP

View full text Add to dashboard Cite

The benzanthrone fluorescent dyes are known as environmentally-sensitive reporters for exploring the physicochemical properties and structural alterations of lipid membranes. In the present work the 100-ns molecular dynamics simulation (MD) was used to characterize the bilayer location and the nature of interactions between the benzanthrone fluorescent dye ABM and the model lipid membranes composed of the zwitterionic lipid phosphatidylcholine (PC) and its mixtures with the anionic lipid phosphatidylglycerol (PG20) and sterol cholesterol (Chol30). The MD simulations were performed in the CHARMM36m force field using the GROMACS package. The ABM molecule, which was initially placed at a distance of 30 Å from the midplane of the lipid bilayer, after 10 ns of simulation was found to be completely incorporated into the membrane interior and remained within the lipid bilayer for the rest of the simulation time. The analysis of the MD simulation results showed that the lipid bilayer location of the benzanthrone dye ABM depends on the membrane composition, with the distance from bilayer center being gradually shifted from 0.78 nm in the neat PC bilayer to 0.95 nm and 1.5 nm in the PG- and Chol-containing membranes, respectively. In addition, the partitioning of the ABM into the neat PC bilayer was followed by the probe translocation from the outer membrane leaflet to the inner one. A separate series of MD simulations was aimed at examining the ABM influence on the lipid bilayer structure. It was found that ABM partitioning into the lipid bilayers of various composition has no significant effect on the orientation of the fatty acid chains and leads only to a small increase of the deuterium order parameter for the carbon atoms 5-to-8 in the sn-2 acyl chains of the neat PC membranes. In addition, the interaction of the ABM with the model lipid membranes caused the slight decrease of the surface area per lipid pointing to the slight increase of the packing density of lipid molecules in the presence of ABM. The results obtained provide a basis for deeper understanding of the membrane interactions of benzanthrone dyes and may be useful for the design of the novel fluorescent probes for membrane studies.

show abstract

Section: Resultsmentioning

confidence: 99%

Molecular Dynamics Simulation of the Interaction Between Benzanthrone Dye and Model Lipid Membranes

Zhytniakivska

2020

EEJP

View full text Add to dashboard Cite

show abstract

Binding of Benzanthrone Dye ABM to Insulin Amyloid Fibrils: Molecular Docking and Molecular Dynamics Simulation Studies

Vus

2020

EEJP

View full text Add to dashboard Cite

The binding of the benzanthrone dye ABM to the model amyloid fibrils of human insulin, referred to here as vealyl (12-VEALYL-17, insulin B-chain)), lyqlen (13-LYQLEN-18, insulin A-chain) and Insf ( 11-LVEALYL-17, B-chain) + 12-SLYQLENY-19, A-chain) was studied by the molecular docking and molecular dynamics simulations. To obtain the relaxed structures with the enhanced conformational stability, the model fibril structures were solvated and equilibrated in water at 300-310 K using the Gromacs simulation package, with backbone position restraints being applied to prevent the beta-sheet disruption. It appeared that the vealyl fibril relaxation resulted in the twisting of the two β-sheets, and only the vealyl fibril remained stable during 20 ns MD simulations of the relaxed structures. Next, Insf, vealyl, lyqlen, and vealyl (relaxed) fibrils were used for the molecular docking studies (by SwissDock), revealing the binding modes of ABM and standard amyloid marker Thioflavin T (ThT) to the examined fibril structures. Specifically, in the most energetically stable complex the vealyl (relaxed) fibril binding site for ABM was located on the dry steric zipper interface, although the dye was associated with only one twisted β-sheet. During the 20 ns MD simulation the ABM fibril location was changed to a deeper position in the dry interface between the two β-sheets, with the dye-interacting residues being represented by 6 LEU, 3 VAL, 2 ALA, 1 TYR and 1 GLU. The binging free energy Δ(Gbinding) for ABM complexation with vealyl (relaxed) fibril evaluated with the GMXPBSA GROMACS tool was found to be –31.4±1.8 kJ/mol, that is in accordance with our estimates derived from the fluorescence studies for ABM binding to the bovine insulin amyloid fibrils Δ(Gbinding)= –30.2 kJ/mol. The Lennard-Jones component appeared to dominate the dye-fibril interactions, with much smaller contributions of Coulombic and nonpolar solvation terms to the total Δ(Gbinding) value, and unfavorable effect of the polar solvation term. These findings indicate that a high specificity of ABM to the insulin amyloid fibrils may arise predominantly from the dye-protein hydrophobic interactions, followed by the formation of van der Waals contacts, thus providing additional evidence for sensitivity of the dye spectral properties to environmental polarity, suggested in our previous studies. Overall, the obtained results provided further insights into the atomistic mechanism of the ABM binding to insulin amyloid fibrils and can be used for development of the novel fluorescent reporters possessing high sensitivity to the amyloid assemblies.

show abstract

Interactions of Novel Phosphonium Dye with Lipid Bilayers: A Fluorescence Study

Zhytniakivska

2021

EEJP

View full text Add to dashboard Cite

The phosphonium-based optical probes attract ever growing interest due to their excellent chemical and photophysical stability, high aqueous solubility, long wavelength absorption and emission, large extinction coefficient, high fluorescence quantum yield, low cytotoxicity, etc. The present study was focused on assessing the ability of the novel phosphonium dye TDV to monitor the changes in physicochemical properties of the model lipid membranes. To this end, the fluorescence spectral properties of TDV have been explored in lipid bilayers composed of zwitterionic lipid phosphatidylcholine (PC) and its mixtures with cholesterol (Chol) or/and anionic phospholipid cardiolipin (CL). It was observed that in the buffer solution TDV possesses one well-defined fluorescence peak with the emission maximum at 533 nm. The dye transfer from the aqueous to lipid phase was followed by the enhancement of the fluorescence intensity coupled with a red shift of the emission maximum up to 67 nm, depending on the liposome composition. The quantitative information about the dye partitioning into lipid phase of the model membranes was obtained through approximating the experimental dependencies of the fluorescence intensity increase vs lipid concentration by the partition model. Analysis of the partition coefficients showed that TDV has a rather high lipid-associating ability and displays sensitivity to the changes in physicochemical properties of the model lipid membranes. The addition of CL, Chol or both lipids to the PC bilayer gives rise to the increase of the TDV partition coefficients compared to the neat PC membranes. The enhancement of the phosphonium dye partitioning in the CL and Chol-containing lipid bilayers has been attributed to the cardiolopin- and cholesterol-induced changes in the structure and physicochemical characteristics of the polar membrane region.

show abstract

Molecular Dynamics Study of Cytochrome C – Lipid Complexes

Cited by 4 publications

References 55 publications

Molecular Dynamics Simulation of the Interaction Between Benzanthrone Dye and Model Lipid Membranes

Molecular Dynamics Simulation of the Interaction Between Benzanthrone Dye and Model Lipid Membranes

Binding of Benzanthrone Dye ABM to Insulin Amyloid Fibrils: Molecular Docking and Molecular Dynamics Simulation Studies

Interactions of Novel Phosphonium Dye with Lipid Bilayers: A Fluorescence Study

Contact Info

Product

Resources

About