Counting the monomers in nanometer-sized oligomers by pulsed electron-electron double resonance

In a lot of cases active biomolecules are complexes of higher order, thus methods capable of counting the number of building blocks and elucidating their geometric arrangement are needed. Therefore, we experimentally validate here spin-counting via 4-pulse electron-electron double resonance (PELDOR) on well-defined test samples. Two biradicals, a symmetric and an asymmetric triradical, and a tetraradical were synthesized in a convergent reaction scheme via palladium-catalyzed cross-coupling reactions. PELDOR was then used to obtain geometric information and the number of spin centers per molecule in a single experiment. The measurement yielded the expected distances (2.2-3.8 nm) and showed that different spin-spin distances in one molecule can be resolved even if the difference amounts to only 5 A. The number of spins n has been determined to be 2.1 in both biradicals, to 3.1 and 3.0 in the symmetric and asymmetric triradicals, respectively, and to 3.9 in the tetraradical. The overall error of PELDOR spin-counting was found to be 5% for up to four spins. Thus, this method is a valuable tool to determine the number of constituting spin-bearing monomers in biologically relevant homo- and heterooligomers and how their oligomerization state and geometric arrangement changes during function.     

Backbone building from quadrilaterals: a fast and accurate algorithm for protein backbone reconstruction from alpha carbon coordinates

In this contribution, we present an algorithm for protein backbone reconstruction that comprises very high computational efficiency with high accuracy. Reconstruction of the main chain atomic coordinates from the alpha carbon trace is a common task in protein modeling, including de novo structure prediction, comparative modeling, and processing experimental data. The method employed in this work follows the main idea of some earlier approaches to the problem. The details and careful design of the present approach are new and lead to the algorithm that outperforms all commonly used earlier applications. BBQ (Backbone Building from Quadrilaterals) program has been extensively tested both on native structures as well as on near-native decoy models and compared with the different available existing methods. Obtained results provide a comprehensive benchmark of existing tools and evaluate their applicability to a large scale modeling using a reduced representation of protein conformational space. The BBQ package is available for downloading from our website at http://biocomp.chem.uw.edu.pl/services/BBQ/. This webpage also provides a user manual that describes BBQ functions in detail.     

Error estimates for the Ginzburg-Landau approximation: an overview and recent results

We consider quasilinear parabolic systems posed on the real line with a spatially homogeneous ground state which becomes unstable via a Hopf-, Turing-, or Turing-Hopf instability. Then close to the first instability via multiple scaling analysis a Ginzburg-Landau equation can be derived in order to describe bifurcating solutions which are slow modulations in time and space of the most unstable modes. We give an overview about the mathematical justification and explain recent error estimates. (© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Comparison of Statistical Descriptors for the Construction of Statistically Similar RVEs

A method for the construction of three-dimensional statistically similar representative volume elements (SSRVEs) is presented. Since the beneficial material properties of microheterogeneous materials originate in the microstructure, its incorporation in material modeling is desired. The FE₂ method is a suitable tool to accomplish this step. Applying this method, a microscopic boundary value problem, given by a representative volume element (RVE) is attached to every integration point of the macroscale. Such RVEs taken from real microstructures exhibit a high level of complexity, thus raise computational costs. The use of a SSRVE with lower complexity is able to decrease these costs. Here, different statistical measures are compared in view of the performance in the SSRVE construction procedure. (© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Maximal Regularity for Non-Autonomous Second Order Cauchy Problems

We consider non-autonomous wave equations $$\left\{\begin{array}{ll}\ddot{u}(t) + \mathcal{B}(t) \dot{u}(t) + \mathcal{A}(t)u(t) = f(t) \quad t{\text -}{\rm a.e.}\\ u(0) = u_{0},\, \dot{u}(0) = u_{1}.\\\end{array}\right.$$ where the operators ${\mathcal{A}(t)}$ and ${\mathcal{B}(t)}$ are associated with time-dependent sesquilinear forms ${\mathfrak{a}(t, ., .)}$ and ${\mathfrak{b}}$ defined on a Hilbert space H with the same domain V. The initial values satisfy ${u_0 \in V}$ and ${u_1 \in H}$ . We prove well-posedness and maximal regularity for the solution both in the spaces V′ and H. We apply the results to non-autonomous Robin-boundary conditions and also use maximal regularity to solve a quasilinear problem.     

Predicting Michael-acceptor reactivity and toxicity through quantum chemical transition-state calculations

The electrophilic reactivity of Michael acceptors is an important determinant of their toxicity. For a set of 35 α,β-unsaturated aldehydes, ketones and esters with experimental rate constants of their reaction with glutathione (GSH), k(GSH), quantum chemical transition-state calculations of the corresponding Michael addition of the model nucleophile methane thiol (CH(3)SH) have been performed at the B3LYP/6-31G** level, focusing on the 1,2-olefin addition pathway without and with initial protonation. Inclusion of Boltzmann-weighting of conformational flexibility yields intrinsic reaction barriers ΔE(?) that for the case of initial protonation correctly reflect the structural variation of k(GSH) across all three compound classes, except that they fail to account for a systematic (essentially incremental) decrease in reactivity upon α-substitution. By contrast, the reduction in k(GSH) through β-substitution is well captured by ΔE(?). Empirical correction for the α-substitution effect yields a high squared correlation coefficient (r(2) = 0.96) for the quantum chemical prediction of log k(GSH), thus enabling an in silico screening of the toxicity-relevant electrophilicity of α,β-unsaturated carbonyls. The latter is demonstrated through application of the calculation scheme for a larger set of 46 Michael-acceptor aldehydes, ketones and esters with experimental values for their toxicity toward the ciliates Tetrahymena pyriformis in terms of 50% growth inhibition values after 48 h exposure (EC(50)). The developed approach may add in the predictive hazard evaluation of α,β-unsaturated carbonyls such as for the European REACH (Registration, Evaluation, Authorization and Restriction of Chemicals) Directive, enabling in particular an early identification of toxicity-relevant Michael-acceptor reactivity.     

Constructing simple yet accurate potentials for describing the solvation of HCl/water clusters in bulk helium and nanodroplets

The infrared spectroscopy of molecules, complexes, and molecular aggregates dissolved in superfluid helium clusters, commonly called HElium NanoDroplet Isolation (HENDI) spectroscopy, is an established, powerful experimental technique for extracting high resolution ro-vibrational spectra at ultra-low temperatures. Realistic quantum simulations of such systems, in particular in cases where the solute is undergoing a chemical reaction, require accurate solute-helium potentials which are also simple enough to be efficiently evaluated over the vast number of steps required in typical Monte Carlo or molecular dynamics sampling. This precludes using global potential energy surfaces as often parameterized for small complexes in the realm of high-resolution spectroscopic investigations that, in view of the computational effort imposed, are focused on the intermolecular interaction of rigid molecules with helium. Simple Lennard-Jones-like pair potentials, on the other hand, fall short in providing the required flexibility and accuracy in order to account for chemical reactions of the solute molecule. Here, a general scheme of constructing sufficiently accurate site-site potentials for use in typical quantum simulations is presented. This scheme employs atom-based grids, accounts for local and global minima, and is applied to the special case of a HCl(H(2)O)(4) cluster solvated by helium. As a first step, accurate interaction energies of a helium atom with a set of representative configurations sampled from a trajectory following the dissociation of the HCl(H(2)O)(4) cluster were computed using an efficient combination of density functional theory and symmetry-adapted perturbation theory, i.e. the DFT-SAPT approach. For each of the sampled cluster configurations, a helium atom was placed at several hundred positions distributed in space, leading to an overall number of about 400,000 such quantum chemical calculations. The resulting total interaction energies, decomposed into several energetic contributions, served to fit a site-site potential, where the sites are located at the atomic positions and, additionally, pseudo-sites are distributed along the lines joining pairs of atom sites within the molecular cluster. This approach ensures that this solute-helium potential is able to describe both undissociated molecular and dissociated (zwitter-) ionic configurations, as well as the interconnecting reaction pathway without re-adjusting partial charges or other parameters depending on the particular configuration. Test calculations of the larger HCl(H(2)O)(5) cluster interacting with helium demonstrate the transferability of the derived site-site potential. This specific potential can be readily used in quantum simulations of such HCl/water clusters in bulk helium or helium nanodroplets, whereas the underlying construction procedure can be generalized to other molecular solutes in other atomic solvents such as those encountered in rare gas matrix isolation spectroscopy.     

Surface-enhanced ATR-IR spectroscopy with interface-grown plasmonic gold-island films near the percolation threshold

Flat nano-island films prepared by wet-chemical deposition were investigated with attenuated total reflection infrared (ATR-IR) spectroscopy and scanning electron microscopy (SEM) in order to analyze the correlation between film morphology and optical properties. Here we choose Au as representative coinage metal (Au, Ag, Cu) that shows strong structure-dependent surface-enhanced infrared absorption (SEIRA). Infrared spectra of octadecanethiol monolayers on films of different stages of morphologic development show effects that are characteristic for SEIRA, such as enhanced vibrational signals, Fano-type line shape, and adsorbate induced baseline shifts. Their extent was found to be strongly dependent on the structural details and the strongest enhancement occurs at the percolation threshold of the two-dimensional island system. Also films beyond percolation show significant enhancement due to residual nanoholes that are acting as hotspots.     

Mechanical detection of ultraslow,Debye‐like Li‐ion motions in LiAlO single crystals

Single crystalline LiAlO is known as a very poor ion conductor. Thus, in its crystalline form it unequivocally disqualifies itself from being a powerful solid electrolyte in modern energy storage systems. On the other hand, its interesting crystal structure proves beneficial to sharpen our understanding of Li ion dynamics in solids which in return might influence application‐oriented research. LiAlO allows us to apply and test techniques that are sensitive to extremely slow Li ion dynamics. This helps us clarifying their diffusion behaviour from a fundamental point of view. Here, we combined two techniques to follow Li ion translational hopping in LiAlO that can be described by the same physical formalism: dynamic mechanical relaxation and electrical relaxation, i.e., ionic conductivity measurements. Via both methods we were able to track the same transport mechanism in LiAlO. Moreover, this enabled us to directly probe extremely slow Li exchange rates at temperatures slightly above 430 K. The results were compared with recent insights from nuclear magnetic resonance spectroscopy. Altogether, an Arrhenius‐type Li diffusion process with an activation energy of ca. 1.12 eV was revealed over a large dynamic range covering 10 orders of magnitude, i.e., spanning a dynamic range from the nano‐second time scale down to the second time scale.