Comparison of available computational studies of the interaction of C₆₀ with lipid bilayer.

<p>Comparison of available computational studies of the interaction of C₆₀ with lipid bilayer.</p

D₃ stereoisomer of tris-malonic fullereneB

<p>A. Free energy profile of the process of the D₃ penetration into the model eukaryotic membrane. B. Orientation (corresponding to the global energy minimum of the free energy profile) of the D₃ molecule adsorbed to the membrane.</p

C₃ stereoisomer of tris-malonic fullerene.

<p>A. Free energy profile of the process of the C₃ penetration into the model eukaryotic membrane. B. Intermediate orientation of the C₃ molecule adsorbed to the membrane with its solvent shell retained. C. Stable conformation (corresponding to the global energy minimum of the free energy profile) of C₃ adsorbed to the membrane and established hydrophobic contact with the lipid tails region.</p

Properties of the DPPC membrane in simulations with different amount of fullerenes.

<p>Properties of the DPPC membrane in simulations with different amount of fullerenes.</p

Comparative Computational Study of Interaction of C₆₀-Fullerene and Tris-Malonyl-C₆₀-Fullerene Isomers with Lipid Bilayer: Relation to Their Antioxidant Effect

<div><p>Oxidative stress induced by excessive production of reactive oxygen species (ROS) has been implicated in the etiology of many human diseases. It has been reported that fullerenes and some of their derivatives–carboxyfullerenes–exhibits a strong free radical scavenging capacity. The permeation of C₆₀-fullerene and its amphiphilic derivatives–C₃-tris-malonic-C₆₀-fullerene (C₃) and D₃-tris-malonyl-C₆₀-fullerene (D₃)–through a lipid bilayer mimicking the eukaryotic cell membrane was studied using molecular dynamics (MD) simulations. The free energy profiles along the normal to the bilayer composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) for C₆₀, C₃ and D₃ were calculated. We found that C₆₀ molecules alone or in clusters spontaneously translocate to the hydrophobic core of the membrane and stay inside the bilayer during the whole period of simulation time. The incorporation of cluster of fullerenes inside the bilayer changes properties of the bilayer and leads to its deformation. In simulations of the tris-malonic fullerenes we discovered that both isomers, C₃ and D₃, adsorb at the surface of the bilayer but only C₃ tends to be buried in the area of the lipid headgroups forming hydrophobic contacts with the lipid tails. We hypothesize that such position has implications for ROS scavenging mechanism in the specific cell compartments.</p></div

Characteristics of fullerene-membrane interactions.

<p>A. Distance between the center of mass (COM) of C₆₀ and COM of the membrane. On the third nanosecond fullerene spontaneously “jump” into the membrane (the membrane surface is shown with the dot line). B. Free energy profile of the process of the C₆₀ penetration into the model eukaryotic membrane. Potential wall at 30 Å is shown as the dotted line. C. Snapshot of the system with a single C₆₀ molecule inside the membrane.</p

Signaling and Adaptation Modulate the Dynamics of the Photosensoric Complex of <i>Natronomonas pharaonis</i>

<div><p>Motile bacteria and archaea respond to chemical and physical stimuli seeking optimal conditions for survival. To this end transmembrane chemo- and photoreceptors organized in large arrays initiate signaling cascades and ultimately regulate the rotation of flagellar motors. To unravel the molecular mechanism of signaling in an archaeal phototaxis complex we performed coarse-grained molecular dynamics simulations of a trimer of receptor/transducer dimers, namely <i>Np</i>SRII/<i>Np</i>HtrII from <i>Natronomonas pharaonis</i>. Signaling is regulated by a reversible methylation mechanism called adaptation, which also influences the level of basal receptor activation. Mimicking two extreme methylation states in our simulations we found conformational changes for the transmembrane region of <i>Np</i>SRII/<i>Np</i>HtrII which resemble experimentally observed light-induced changes. Further downstream in the cytoplasmic domain of the transducer the signal propagates via distinct changes in the dynamics of HAMP1, HAMP2, the adaptation domain and the binding region for the kinase CheA, where conformational rearrangements were found to be subtle. Overall these observations suggest a signaling mechanism based on dynamic allostery resembling models previously proposed for <i>E</i>. <i>coli</i> chemoreceptors, indicating similar properties of signal transduction for archaeal photoreceptors and bacterial chemoreceptors.</p></div

Dynamics of the methylated and the demethylated systems.

<p>A: Structure of the <i>Np</i>SRII/<i>Np</i>HtrII trimeric complex with colors that code for the difference between the RMSF value per residue of the demethylated and the methylated transducer. Positive values (in Å) correspond to a higher fluctuation and therefore higher mobility of the corresponding residues in the demethylated system, negative values indicate a lower mobility. B: The differences in mobility as function of residue number show distinct changes in the transmembrane region of the complex, an inversion between the two HAMP domains and in the adaptation and close to the glycine rich (293, 296) regions. This change in dynamics upon adaption includes the tip region and the binding sites for CheA (A/W). Colored bars have the same meaning as in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004561#pcbi.1004561.g003" target="_blank">Fig 3</a>.</p

Inter-dimeric distances for related residues of the transducer.

<p>Distances were calculated as an average over the three dimers for the methylated (black) and demethylated (red) states, shaded areas representing the standard deviation. The distance is measured between the center of mass (COM) of two related residues in one dimer and the COM of the six respective residues in the trimer-of-dimers (see inset on the lower left). The domains of the complex are depicted in colored bars; m.s and A/W indicate methylation sites and binding sites for CheA/CheW, respectively. Representative distance trajectories are depicted in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004561#pcbi.1004561.s007" target="_blank">S7 Fig</a>.</p

Two component phototaxis system of <i>N</i>. <i>pharaonis</i>.

<p><i>Np</i>SRII/<i>Np</i>HtrII dimers are the basic elements of photoreceptor complexes in <i>N</i>. <i>pharaonis</i>. They consist of two sensory rhodopsins, <i>Np</i>SRII, and two transducer proteins, <i>Np</i>HtrII, mostly of α-helical secondary structure, with a characteristic domain organization. Light activation of <i>Np</i>SRII induces conformational and/or dynamical changes in the transducer which are converted by two HAMP domains and conveyed along the 20 nm long transducer to the tip region, where it activates the homodimeric histidine kinase CheA bound together with the adapter protein CheW. The kinase CheA undergoes auto-phosphorylation and further transfers the phosphate group to the response regulators CheY or CheB. CheY affects the rotational bias of the flagellar motor, while the methylesterase CheB along with the methyltransferase CheR controls the adaptation (feedback) mechanism. The related chemoreceptor and most likely also the photoreceptor dimers further organize into trimers, which, together with CheA and CheW, lead to the formation of large sensor arrays.</p