Quantum Mechanical/Molecular Mechanical Study on the Enantioselectivity of the Enzymatic Baeyer–Villiger Reaction of 4-Hydroxycyclohexanone

We report a combined quantum mechanical/molecular mechanical (QM/MM) study of the effect of mutations of the Phe434 residue in the active site of cyclohexanone monooxygenase (CHMO) on its enantioselectivity toward 4-hydroxycyclohexanone. In terms of our previously established model of the enzymatic Baeyer–Villiger reaction, enantioselectivity is governed by the preference toward the equatorial ((S)-selectivity) or axial ((R)-selectivity) conformation of the substituent at the C4 carbon atom of the cyclohexanone ring in the Criegee intermediate and the subsequent rate-limiting transition state for migration (TS2). We assess the enantiopreference by locating all relevant TS2 structures at the QM/MM level. In the wild-type enzyme we find that the axial conformation is energetically slightly more stable, thus leading to a small excess of (R)-product. In the Phe434Ser mutant, there is a hydrogen bond between the serine side chain and the equatorial substrate hydroxyl group that is retained during the whole reaction, and hence there is pronounced reverse (S)-enantioselectivity. Another mutant, Phe434Ile, is shown to preserve and enhance the (R)-selectivity. All these findings are in accordance with experiment. The QM/MM calculations allow us to explain the effect of point mutations on CHMO enantioselectivity for the first time at the molecular level by an analysis of the specific interactions between substrate and active-site environment in the TS2 structures that satisfy the basic stereoelectronic requirement of anti-periplanarity for the migrating σ-bond

NLTE effects on Fe I/II in the atmospheres of FGK stars and application to abundance analysis of their spectra

We describe the first results from our project aimed at large-scale calculations of NLTE abundance corrections for important astrophysical atoms and ions. In this paper, the focus is on Fe which is a proxy of stellar metallicity and is commonly used to derive effective temperature and gravity. We present a small grid of NLTE abundance corrections for Fe I lines and discuss how NLTE effects influence determination of effective temperature, surface gravity, and metallicity for late-type stars.Comment: 6 pages, to be published in IOP The Journal of Physics: Conference Series, proceedings of the Workshop: 'Stellar Atmospheres in the Gaia Era: Quantitative Spectroscopy and Comparative Spectrum Modelling', Brussels, June 201

Особливості змісту права громадян на екологічну безпеку

В статье сделан анализ содержания права граждан на экологическую безопасность, определяется момент, с которого право на экологическую безопасность считается нарушенным

Directed evolution of an enantioselective Bacillus subtilis lipase

Chiral compounds are of steadily increasing importance to the chemical industry, in particular for the production of pharmaceuticals. Where do these compounds come from? Apart from natural resources, two synthetic strategies are available: asymmetric chemical catalysis using transition metal catalysts and biocatalysis using enzymes. In the latter case, screening programs have identified a number of enzymes. However, their enantioselectivity is often not high enough for a desired reaction. This problem can be solved by applying directed evolution to create enantioselective enzymes as shown here for a lipase from Bacillus subtilis. The reaction studied was the asymmetric hydrolysis of meso-1,4-diacetoxy-2-cyclopentene with the formation of chiral alcohols which were detected by electrospray ionization mass spectrometry. Iterative cycles of random mutagenesis and screening allowed the identification of several variants with improved enantioselectivities. In parallel, we have started to use X-ray structural data to simulate the Bacillus subtilis lipase A-catalyzed substrate hydrolysis by using quantum mechanical and molecular mechanical calculations. This combined approach should finally enable us to devise more efficient strategies for the directed evolution of enantioselective enzymes

Algorithmic Interpretations of Fractal Dimension

We study algorithmic problems on subsets of Euclidean space of low fractal dimension. These spaces are the subject of intensive study in various branches of mathematics, including geometry, topology, and measure theory. There are several well-studied notions of fractal dimension for sets and measures in Euclidean space. We consider a definition of fractal dimension for finite metric spaces which agrees with standard notions used to empirically estimate the fractal dimension of various sets. We define the fractal dimension of some metric space to be the infimum delta>0, such that for any eps>0, for any ball B of radius r >= 2eps, and for any eps-net N, we have |B cap N|=O((r/eps)^delta). Using this definition we obtain faster algorithms for a plethora of classical problems on sets of low fractal dimension in Euclidean space. Our results apply to exact and fixed-parameter algorithms, approximation schemes, and spanner constructions. Interestingly, the dependence of the performance of these algorithms on the fractal dimension nearly matches the currently best-known dependence on the standard Euclidean dimension. Thus, when the fractal dimension is strictly smaller than the ambient dimension, our results yield improved solutions in all of these settings. We remark that our definition of fractal definition is equivalent up to constant factors to the well-studied notion of doubling dimension. However, in the problems that we consider, the dimension appears in the exponent of the running time, and doubling dimension is not precise enough for capturing the best possible such exponent for subsets of Euclidean space. Thus our work is orthogonal to previous results on spaces of low doubling dimension; while algorithms on spaces of low doubling dimension seek to extend results from the case of low dimensional Euclidean spaces to more general metric spaces, our goal is to obtain faster algorithms for special pointsets in Euclidean space

Rabi oscillations between ground and Rydberg states and van der Waals blockade in a mesoscopic frozen Rydberg gas

We present a detailed analysis of our recent observation of synchronous Rabi oscillations between the electronic ground state and Rydberg states in a mesoscopic ensemble containing roughly 100 ultracold atoms [M. Reetz-Lamour \textit{et al.}, submitted, arXiv:0711.4321]. The mesoscopic cloud is selected out of a sample of laser-cooled Rb atoms by optical pumping. The atoms are coupled to a Rydberg state with principal quantum number around 30 by a two-photon scheme employing flat-top laser beams. The influence of residual spatial intensity fluctuations as well as sources of decoherence such as redistribution to other states, radiative lifetime, and laser bandwidth are analysed. The results open up new possibilities for the investigation of coherent many-body phenomena in dipolar Rydberg gases. As an example we demonstrate the van der Waals blockade, a variant of the dipole blockade, for a mesoscopic atom sample

Measurement of the electric dipole moments for transitions to rubidium Rydberg states via Autler-Townes splitting

We present the direct measurements of electric-dipole moments for $5P_{3/2}\to nD_{5/2}$ transitions with $20<n<48$ for Rubidium atoms. The measurements were performed in an ultracold sample via observation of the Autler-Townes splitting in a three-level ladder scheme, commonly used for 2-photon excitation of Rydberg states. To the best of our knowledge, this is the first systematic measurement of the electric dipole moments for transitions from low excited states of rubidium to Rydberg states. Due to its simplicity and versatility, this method can be easily extended to other transitions and other atomic species with little constraints. Good agreement of the experimental results with theory proves the reliability of the measurement method.Comment: 12 pages, 6 figures; figure 6 replaced with correct versio

A planar multipole ion trap

We report on the realisation of a chip-based multipole ion trap manufactured using micro-electromechanical systems (MEMS) technology. It provides ion confinement in an almost field-free volume between two planes of radiofrequency electrodes, deposited on glass substrates, which allows for optical access to the trap. An analytical model of the effective trapping potential is presented and compared with numerical calculations. Stable trapping of argon ions is achieved and a lifetime of 16s is measured. Electrostatic charging of the chip surfaces is studied and found to agree with a numerical estimate

GLUE-IT and PEDEL-AA: new programmes for analyzing protein diversity in randomized libraries

There are many methods for introducing random mutations into nucleic acid sequences. Previously, we described a suite of programmes for estimating the completeness and diversity of randomized DNA libraries generated by a number of these protocols. Our programmes suggested some empirical guidelines for library design; however, no information was provided regarding library diversity at the protein (rather than DNA) level. We have now updated our web server, enabling analysis of translated libraries constructed by site-saturation mutagenesis and error-prone PCR (epPCR). We introduce GLUE-Including Translation (GLUE-IT), which finds the expected amino acid completeness of libraries in which up to six codons have been independently varied (according to any user-specified randomization scheme). We provide two tools for assisting with experimental design: CodonCalculator, for assessing amino acids corresponding to given randomized codons; and AA-Calculator, for finding degenerate codons that encode user-specified sets of amino acids. We also present PEDEL-AA, which calculates amino acid statistics for libraries generated by epPCR. Input includes the parent sequence, overall mutation rate, library size, indel rates and a nucleotide mutation matrix. Output includes amino acid completeness and diversity statistics, and the number and length distribution of sequences truncated by premature termination codons. The web interfaces are available at http://guinevere.otago.ac.nz/stats.html

Analysis of stellar spectra with 3D and NLTE models

Models of radiation transport in stellar atmospheres are the hinge of modern astrophysics. Our knowledge of stars, stellar populations, and galaxies is only as good as the theoretical models, which are used for the interpretation of their observed spectra, photometric magnitudes, and spectral energy distributions. I describe recent advances in the field of stellar atmosphere modelling for late-type stars. Various aspects of radiation transport with 1D hydrostatic, LTE, NLTE, and 3D radiative-hydrodynamical models are briefly reviewed.Comment: 21 pages, accepted for publication as a chapter in "Determination of Atmospheric Parameters of B, A, F and G Type Stars", Springer (2014), eds. E. Niemczura, B. Smalley, W. Pyc