Cholesterol and melatonin regulated membrane fluidity does not affect the membrane breakage triggered by amyloid-beta peptide.

We have studied by means of small angle neutron scattering and diffraction, and molecular dynamics simulations the effect of lipid membrane fluidity on the amyloid-beta peptide interactions with the membrane. These interactions have been discovered previously to trigger the reorganization of model membranes between unilamellar vesicles and planar membranes (bicelle-like structures) during the lipid phase transition. The morphology changes were taking place in rigid membranes prepared of fully saturated lipids and were proposed to play a role in the onset of amyloid related disorders. We show in this study that the replacement of fully saturated lipids by more fluid mono-unsaturated lipids eliminates the mentioned morphology changes, most likely due to the absence of phase transition within the temperature range investigated. We have therefore controlled the membrane rigidity also while ensuring the presence of membrane phase transition within the biologically relevant temperatures. It was done by the addition of melatonin and/or cholesterol to the initial membranes made of saturated lipids. Small angle neutron scattering experiments performed over a range of cholesterol and melatonin concentrations show their distinctive effects on the local membrane structure only. The cholesterol for example affects the membrane curvature such that spontaneously formed unilamellar vesicles are of much larger sizes than those formed by the neat lipid membranes or membranes with melatonin added. The temperature dependent experiments, however, reveal no influence on the previously discovered membrane breakage whether cholesterol or melatonin have been added.

On Correlation Effect of the Van-der-Waals and Intramolecular Forces for the Nucleotide Chain - Metallic Nanoparticles - Carbon Nanotube Binding.

BACKGROUND: The tertiary system of nucleotide chain (NC) - gold nanoparticles (NPs) - carbon nanotube (CNT) represents a great interest in the modern research and application of the bio-nano-technologies. The application aspects include, for example, the development of electronic mobile diagnostic facilities, nanorobotic design for a drug delivery inside living cell, and so on. The small NC chain represents an important stage in the understanding of the interaction mechanism of a full DNA or RNA molecule with NP and CNT. In this regard, one has to mention the development of the DNA-CNT devices for the purposes of diagnostic applications in the chemical or drug delivery. METHODS: For the NC-NP-CNT system, we have built up a series of the molecular dynamics (MD) models with different NC-NP configurations and performed their MD analysis. The entire system (the NC chain, gold NPs and CNT) was allowed to interact with each other by the only VdW forces. The Lennard-Jones short-ranged interaction was assumed between the NC, NP and CNT. For the CNT a many body Tersoff potential having a quantum-chemistry nature was used. So far, the so-called hybrid MD approach was realized, where the quantum-chemistry potential in combination with a classical trajectory calculation applied . RESULTS: The peculiarities of the NC-NP interaction and bond formation inside of a CNT matrix were investigated along with the structural and dynamical behavior. The correlation effects between the weak Van der Waals (VdW) forces and intramolecular vibrations were enlighten for the molecular system consisting of a small nucleotide chain (NC), gold nanoparticles (NPs) and carbon nanotube (CNT) using molecular dynamics (MD) simulation method. CONCLUSION: The NC intermolecular motions were estimated from MD data thereby building the distance distributions, the angular and dihedral (torsional) bond energy graphs versus simulation time at different temperatures from T=100 K up to 300 K. The MD simulation results have shown that depending on the relative NC-NP position a different scenario of bonding between the NC-NP, within CNT matrix, is possible. We have observed the possibilities of formation of weak, strong and intermediate bonds between the NP-NC, which are overestimated by a presence of CNT matrix as confined environment. The NC chain can form with a particular gold atom a close contact, while with another under the same positional and temperature conditions the weak resultant bonding formation might be possible. We estimated the fluctuations in the NP-NC bonding processes for a single gold atomic case (models 1-3, NC-1NP-CNT), for the two (model 4-6, NC-2NP-CNT) and three (model 7, NC-3NP-CNT) gold particle ones. Thus, a concurrent effect between the NC intramolecular vibrations and a weak VdW interaction between the NC and gold NP were studied in detail.

[Simulation of Mutant P32T Homo- and Heterodimers of Human Inosine Triphosphate Pyrophosphatase hITPA].

The structure of three forms of a dimeric enzyme, human inosine triphosphate pyrophosphatase, is considered to identify the enzyme conformation changes causing the inactivation effect of a P32T mutation. Analysis of a nanosecond molecular dynamics is performed; the mean square deviations of the atoms between the wild-type and mutant homodimers, and also the heterodimer are calculated. A 3 ns modeling shows a greater displacement of atoms in mutant protomers. During molecular dynamics simulation, the strongest changes are observed in the loop between α2 and ß2 (amino acid residues 28-33, an area of the P32T mutation), the loop between ß5 and ß6, and the C-terminal amino acid residues. The loop between (α2 and ß2 has two conformations characterized by different positions of the Phe31 aromatic group. The distance between Cys33 (Cα) and Phe31 (C(z)) for wild-type and mutant protomers was -9 and 5.5 Å, respectively. These conformations were kept constant.

A Novel Approach to Simulate a Charge Transfer in DNA Repair by an Anacystis nidulans Photolyase.

An Anacystis nidulans photolyase enzyme containing two chromophore cofactors was simulated for a photoreaction DNA repairing process via molecular dynamics (MD) method. A novel approach has been introduced for the electron transfer between the FAD (flavin adenine dinucleotide; flavin) molecule and CPD (cyclobutane pyrimidine dimer). This approach involves four simulation stages with different charges for the FAD and CPD fragments and a role of a charged state of the active cofactor was qualified during the MD modeling. Observations show that flavin has actively participated in a charge transfer process, thereby involving the conformational changes of the DNA and CPD substrate fragment. The DNA conformation behavior has shown to correlate with the electron transfer from flavin to CPD. This is manifested on the similarities of the DNA repairing process by excision repair of the UV photoproducts.