Electromagnetic field modulates aggregation propensity of amyloid peptides.

Nonthermal effects of the electromagnetic (EM) field in the radio and microwave frequency ranges on basic biological matter are difficult to detect and thus remain poorly understood. In this work, all-atom nonequilibrium molecular dynamics simulations were performed to investigate the molecular mechanisms of an amyloidogenic peptide response to nonionizing radiation of varying field characteristics. The results showed that the EM field induced peptide conformations dependent on the field frequency and strength. At the high field strength (0.7 V/nmrms), the peptide explored a wider conformational space as the frequency increased from 1.0 to 5.0 GHz. At the intermediate strength fields (0.07-0.0385 V/nmrms), the frequencies of 1.0 and 2.5 GHz resulted in the peptide being trapped in specific conformations, with 1.0 GHz enabling both fibril-forming and fibril-inhibiting conformations, while 2.5 GHz led to formation of mostly fibril-forming conformations. In contrast, the 5.0 GHz frequency caused increased peptide dynamics and more extended conformations with fibril-enabling aromatic side-chain arrangement akin to the structures formed under ambient conditions. All the simulated frequencies at low strength fields (0.007-0.0007 V/nmrms) resulted in the formation of amyloid-prone hairpin conformations similar to those formed under the weak static electric field and ambient conditions. These results suggest that specific ranges of EM field parameters produce peptide conformations unfavorable for formation of amyloid fibrils, a phenomenon that can be exploited in treatment and prevention of amyloid diseases. Alternatively, EM field parameters can be selected to modulate the formation of well-ordered peptide assemblies as a rational design strategy for engineering biocompatible materials.

Nanomaterials in biological environment: a review of computer modelling studies.

Nanotechnology is set to impact a vast range of fields, including computer science, materials technology, engineering/manufacturing and medicine. As nanotechnology grows so does exposure to nanostructured materials, thus investigation of the effects of nanomaterials on biological systems is paramount. Computational techniques can allow investigation of these systems at the nanoscale, providing insight into otherwise unexaminable properties, related to both the intentional and unintentional effects of nanomaterials. Herein, we review the current literature involving computational modelling of nanoparticles and biological systems. This literature has highlighted the common modes in which nanostructured materials interact with biological molecules such as membranes, peptides/proteins and DNA. Hydrophobic interactions are the most favoured, with π-stacking of the aromatic side-chains common when binding to a carbonaceous nanoparticle or surface. van der Waals forces are found to dominate in the insertion process of DNA molecules into carbon nanotubes. Generally, nanoparticles have been observed to disrupt the tertiary structure of proteins due to the curvature and atomic arrangement of the particle surface. Many hydrophobic nanoparticles are found to be able to transverse a lipid membrane, with some nanoparticles even causing mechanical damage to the membrane, thus potentially leading to cytotoxic effects. Current computational techniques have revealed how some nanoparticles interact with biological systems. However, further research is required to determine both useful applications and possible cytotoxic effects that nanoparticles may have on DNA, protein and membrane structure and function within biosystems.

Effect of oxidation and mutation on the conformational dynamics and fibril assembly of amyloidogenic peptides derived from apolipoprotein C-II.

The oxidation of methionine residues in proteins can inhibit the self-assembly of proteins to form amyloid fibrils. For human apolipoprotein (apo) C-II the oxidation of methionine at position 60 inhibits fibril formation by the mature protein and by the core peptides apoC-II(56-76) and apoC-II(60-70). To investigate the molecular nature of these effects, we carried out fully solvated, all-atom molecular dynamics simulations of the structural changes in apoC-II(56-76) associated with substitutions of oxidized methionine (Met ox) at position 60. The results with apoC-II(56-76) (Met ox) showed less flexibility in structure, leading to a perturbation of the hydrophobic core. Valine substitution at position 60 showed an increased tendency to explore a wide range of conformational space, whereas the behavior of the Gln substitution mutant was similar to the wild-type peptide. These simulations are consistent with kinetic measurements which showed that a Met60Gln substitution within apoC-II(56-76) had little effect on the rate of fibril formation whereas substitution of Met ox or Val at position 60 lead to significant inhibition of peptide fibril formation. The effects of amino acid modification and substitutions on the kinetics of peptide fibril formation differ from the effects observed with full-length apoC-II inferring that additional mechanisms are involved in fibril formation by mature apoC-II.

Adsorption of atomic nitrogen and oxygen on [Formula: see text] surface: a density functional theory study.

The adsorption of atomic nitrogen and oxygen on the ([Formula: see text]) crystal face of zinc oxide (ZnO) was studied. Binding energies, workfunction changes, vibrational frequencies, charge density differences and electron localization functions were calculated. It was elucidated that atomic oxygen binds more strongly than nitrogen, with the most stable [Formula: see text] structure exhibiting a binding energy of -2.47 eV, indicating chemisorption onto the surface. Surface reconstructions were observed for the most stable minima of both atomic species. Positive workfunction changes were calculated for both adsorbed oxygen and nitrogen if the adsorbate interacted with zinc atoms. Negative workfunction changes were calculated when the adsorbate interacted with both surface oxygen and zinc atoms. Interactions between the adsorbate and the surface zinc atoms resulted in ionic-type bonding, whereas interactions with oxygen atoms were more likely to result in the formation of covalent-type bonding. The positive workfunction changes correlate with an experimentally observed increase in resistance of ZnO conductometric sensor devices.

Protein flexibility: multiple molecular dynamics simulations of insulin chain B.

Multiple molecular dynamics simulations totaling more than 100 ns were performed on chain B of insulin in explicit solvent at 300 K and 400 K. Despite some individual variations, a comparison of the protein dynamics of each simulation showed similar trends and most structures were consistent with NMR experimental values, even at the elevated temperature. The importance of packing interactions in determining the conformational transitions of the protein was observed, sometimes resulting in conformations induced by localized hydrophobic interactions. The high temperature simulation generated a more diverse range of structures with similar elements of secondary structure and populated conformations to the simulations at room temperature. A broad sampling of the conformational space of insulin chain B illustrated a wide range of conformational states with many transitions at room temperature in addition to the conformational states observed experimentally. The T-state conformation associated with insulin activity was consistently present and a possible mechanism of behavior was suggested.

Refinements in the collection of energy filtered diffraction patterns from disordered materials.

In this paper a method for collecting electron diffraction patterns using a Gatan imaging filter is presented. The method enables high-quality diffraction data to be measured at scattering angles comparable to those that can be obtained using X-ray and neutron diffraction. In addition, the method offers the capability for examining small regions of sample in, for example, thin films and nano-structures. Using X-ray, neutron and electron diffraction data collected from the same sample, we demonstrate quantitative agreement between all three. We also present a novel method for obtaining the single scattering contribution to the total diffracted intensity by collecting data at various electron wavelengths. This approach allows pair distribution functions to be determined from electron diffraction in cases where there exists significant multiple scattering.

Application of numerical basis sets to hydrogen bonded systems: a density functional theory study.

We have investigated and compared the ability of numerical and Gaussian-type basis sets to accurately describe the geometries and binding energies of a selection of hydrogen bonded systems that are well studied theoretically and experimentally. The numerical basis sets produced accurate results for geometric parameters but tended to overestimate binding energies. However, a comparison of the time taken to optimize phosphinic acid dimer, the largest complex considered in this study, shows that calculations using numerical basis sets offer a definitive advantage where geometry optimization of large systems is required.

Effect of external stresses on protein conformation: a computer modelling study.

The increasing use of digital technologies such as mobile phones has led to major health concerns about the effects of non-ionizing pulsed radiation exposure. We believe that the health implications of exposure to radiation cannot be fully understood without establishing the molecular mechanisms of biological effects of pulsed microwaves. We aim to establish methods for studying the molecular mechanisms of protein structural and energetic changes occurring due to external stresses related to non-ionizing radiation by using a combination of experimental and theoretical approaches. In this paper, we present the results from our fully atomistic simulation study of chemical and thermal stress response of a prototype protein, insulin. We performed a series of molecular dynamics simulations of insulin in solution under equilibrium conditions, under chemical stress (imitated by reducing the disulfide bonds in the protein molecule), and under short-lived thermal stress (imitated by increasing simulation temperature for up to 2 ns). The resultant protein conformational behaviour was analysed for various properties with the aim of establishing analysis routines for classification of protein unfolding pathways and associated molecular mechanisms.