MetaProFi: an ultrafast chunked Bloom filter for storing and querying protein and nucleotide sequence data for accurate identification of functionally relevant genetic variants.

MOTIVATION: Bloom filters are a popular data structure that allows rapid searches in large sequence datasets. So far, all tools work with nucleotide sequences; however, protein sequences are conserved over longer evolutionary distances, and only mutations on the protein level may have any functional significance. RESULTS: We present MetaProFi, a Bloom filter-based tool that, for the first time, offers the functionality to build indexes of amino acid sequences and query them with both amino acid and nucleotide sequences, thus bringing sequence comparison to the biologically relevant protein level. MetaProFi implements additional efficient engineering solutions, such as a shared memory system, chunked data storage and efficient compression. In addition to its conceptual novelty, MetaProFi demonstrates state-of-the-art performance and excellent memory consumption-to-speed ratio when applied to various large datasets. AVAILABILITY AND IMPLEMENTATION: Source code in Python is available at https://github.com/kalininalab/metaprofi.

Lower and upper extremity contributions to propulsion and resistance during semi-tethered load-velocity profiling in front crawl swimming.

The study estimated lower and upper extremity contributions to whole-body front crawl swimming using semi-tethered load-velocity profiling. Nine female and 11 male (inter)national-level swimmers performed 20 m semi-tethered sprints, each with five progressive loads for lower (leg kicking), upper (arm stroke), and whole-body front crawl movements. The theoretical maximal speed (v0) and load (L0), and active drag (Da) were expressed as a percentage of the sum of both extremities for the movements of each extremity to calculate their contributions. The difference of whole-body values minus the sum of both extremities was used to estimate whole-body reserves. Lower (upper) body contributions were 43.8 ± 2.8% (56.2%) for v0, 37.3 ± 7.1% (62.7%) for L0, and 39.6 ± 5.6% (60.4%) for Da. Statistically significant whole-body reserves were found for v0 (-30.9 ± 3.9%, p < 0.001) and Da (-5.7 ± 11.7%, p = 0.04). V0 reserves correlated very highly with whole-body v0 in males (r = 0.71, p = 0.014) and moderately in females (r = 0.47, p = 0.21). The lower extremities contribute substantially to front crawl load-velocity profiles of highly trained swimmers. Higher sprint swimming speeds are associated with an efficient speed transfer from lower- and upper- to whole-body movement.

Modeling lactate threshold in young squad athletes: influence of sex, maximal oxygen uptake, and cost of running.

PURPOSE: This study aimed to investigate: 1. The influence of sex and age on the accuracy of the classical model of endurance performance, including maximal oxygen uptake ([Formula: see text]), its fraction (LT2%), and cost of running (CR), for calculating running speed at lactate threshold 2 (vLT2) in young athletes. 2. The impact of different CR determination methods on the accuracy of the model. 3. The contributions of [Formula: see text], LT2%, and CR to vLT2 in different sexes. METHODS: 45 male and 55 female young squad athletes from different sports (age: 15.4 ± 1.3 years; [Formula: see text]: 51.4 ± 6.8 [Formula: see text]) performed an incremental treadmill test to determine [Formula: see text], LT2%, CR, and vLT2. CR was assessed at a fixed running speed (2.8 [Formula: see text]), at lactate threshold 1 (LT1), and at 80% of [Formula: see text], respectively. RESULTS: Experimentally determined and modeled vLT2 were highly consistent independent of sex and age (ICC [Formula: see text] 0.959). The accuracy of vLT2 modeling was improved by reducing random variation using individualized CR at 80% [Formula: see text] (± 4%) compared to CR at LT1 (± 7%) and at a fixed speed (± 8%). 97% of the total variance of vLT2 was explained by [Formula: see text], LT2%, and CR. While [Formula: see text] and CR showed the highest unique (96.5% and 31.9% of total [Formula: see text], respectively) and common (- 31.6%) contributions to the regression model, LT2% made the smallest contribution (7.5%). CONCLUSION: Our findings indicate: 1. High accuracy of the classical model of endurance performance in calculating vLT2 in young athletes independent of age and sex. 2. The importance of work rate selection in determining CR to accurately predict vLT2. 3. The largest contribution of [Formula: see text] and CR to vLT2, the latter being more important in female athletes than in males, and the least contribution of LT2%.

Learning Extremal Representations with Deep Archetypal Analysis.

Archetypes represent extreme manifestations of a population with respect to specific characteristic traits or features. In linear feature space, archetypes approximate the data convex hull allowing all data points to be expressed as convex mixtures of archetypes. As mixing of archetypes is performed directly on the input data, linear Archetypal Analysis requires additivity of the input, which is a strong assumption unlikely to hold e.g. in case of image data. To address this problem, we propose learning an appropriate latent feature space while simultaneously identifying suitable archetypes. We thus introduce a generative formulation of the linear archetype model, parameterized by neural networks. By introducing the distance-dependent archetype loss, the linear archetype model can be integrated into the latent space of a deep variational information bottleneck and an optimal representation, together with the archetypes, can be learned end-to-end. Moreover, the information bottleneck framework allows for a natural incorporation of arbitrarily complex side information during training. As a consequence, learned archetypes become easily interpretable as they derive their meaning directly from the included side information. Applicability of the proposed method is demonstrated by exploring archetypes of female facial expressions while using multi-rater based emotion scores of these expressions as side information. A second application illustrates the exploration of the chemical space of small organic molecules. By using different kinds of side information we demonstrate how identified archetypes, along with their interpretation, largely depend on the side information provided. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11263-020-01390-3.

Comparison of two different cooling systems in alleviating thermal and physiological strain during prolonged exercise in the heat.

This study compared the efficacy of an ice vest comprising of water (WATER) or a water-carbon (CARBON) emulsion on thermophysiological responses to strenuous exercise in the heat. Twelve male cyclists completed three 50-minute constant workload trials (55% of peak power output, ambient temperature 30.4 ± 0.6°C) with WATER, CARBON, and without ice vest (CONTROL), respectively. The increase in core body temperature (Tcore) was lower in WATER at 40 (-0.49 ± 0.34 °C) and 50 minutes (-0.48 ± 0.48 °C) and in CARBON at 30 (-0.41 ± 0.48 °C), 40 (-0.54 ± 0.51 °C), and 50 minutes (-0.67 ± 0.62 °C) as compared to CONTROL (p < 0.05, ES > 0.8). While heart rate and blood lactate kinetics did not differ between the conditions, statistical main effects in favour of both WATER and CARBON were found for thermal sensation (condition p < 0.001 and interaction p < 0.01) and rating of perceived exertion (condition p < 0.05). Per-cooling with CARBON and WATER similarly reduced Tcore but not physiological strain during prolonged exercise in the heat. Practitioner Summary: Exercise in the heat is characterised by increases in thermophysiological strain. Both per-cooling with a novel carbon-based and a conventional water-based ice vest were shown to reduce core temperature significantly. However, due to its lower mass, the carbon-based system may be recommended especially for weight-bearing sports.

9-Methyl-ß-carboline inhibits monoamine oxidase activity and stimulates the expression of neurotrophic factors by astrocytes.

ß-Carbolines (BC) are pyridoindoles, which can be found in various exogenous and endogenous sources. Recent studies revealed neurostimulative, neuroprotective, neuroregenerative and anti-inflammatory effects of 9-methyl-BC (9-Me-BC). Additionally, 9-me-BC increased neurite outgrowth of dopaminergic neurons independent of dopamine uptake into these neurons. In this study, the role of astrocytes in neurostimulative, neuroregenerative and neuroprotective properties of 9-me-BC was further explored.9-Me-BC exerted anti-proliferative effects without toxic properties in dopaminergic midbrain and cortical astrocyte cultures. The organic cation transporter (OCT) but not the dopamine transporter seem to mediate at least part the effect of 9-me-BC on astrocytes. Remarkably, 9-me-BC stimulated the gene expression of several important neurotrophic factors for dopaminergic neurons like Artn, Bdnf, Egln1, Tgfb2 and Ncam1. These factors are well known to stimulate neurite outgrowth and to show neuroprotective and neuroregenerative properties to dopaminergic neurons against various toxins. Further, we show that effect of 9-me-BC is mediated through phosphatidylinositol 3-kinase (PI3K) pathway. Additionally, 9-me-BC showed inhibitory properties to monoamine oxidase (MAO) activity with an IC50 value of 1 µM for MAO-A and of 15.5 µM for MAO-B. The inhibition of MAO by 9-me-BC might contribute to the observed increased dopamine content and anti-apoptotic properties in cell culture after 9-me-BC treatment in recent studies. Thus, 9-me-BC have a plethora of beneficial effects on dopaminergic neurons warranting its exploration as a new multimodal anti-parkinsonian medication.

Palladium embedded in SnO2 enhances the sensitivity of flame-made chemoresistive gas sensors.

Palladium is used commonly to enhance the performance of chemoresistive metal-oxide gas sensors. Typically, this enhancement is attributed to the presence of Pd clusters on the surface of their metal-oxide support (i.e. SnO2). Possible Pd incorporation or embedding into the support rarely has been considered. Here, SnO2 particles (15 - 21 nm in diameter measured by N2 adsorption) with different Pd contents (0 - 3 mol%) were prepared by flame spray pyrolysis (FSP). Leaching these particles with HNO3 and characterization by inductively coupled plasma - optical emission spectrometry (ICP-OES) indicated that only 36 - 60% of Pd have been removed (e.g., from the SnO2 surface). The rest was embedded within the SnO2 particles. Annealing prior to leaching decreased by ~30% that Pd surface content. Most interestingly, such SnO2 particles (with only embedded Pd) show higher sensor response to acetone, ethanol and CO at 350 °C compared to SnO2 particles containing both surface and embedded Pd (i.e. before leaching). As a result, such sensors can detect acetone with high (> 25) signal-to-noise ratio at levels down to 5 ppb at 50% relative humidity. Graphical abstractFlame-made SnO2 nanoparticles with embedded and surface Pd (triangles) exhibit lower sensor response to acetone, ethanol and CO than SnO2 from which the surface Pd had been removed by leaching (circles).

How to Improve Change-of-Direction Speed in Junior Team Sport Athletes-Horizontal, Vertical, Maximal, or Explosive Strength Training?

Keller, S, Koob, A, Corak, D, von Schöning, V, and Born, DP. How to improve change-of-direction speed in junior team sport athletes-Horizontal, vertical, maximal, or explosive strength training? J Strength Cond Res 34(2): 473-482, 2020-The purpose of the study was to compare the effects of 4 different training methods on change-of-direction (COD) speed in junior team sport athletes. Specifically, we investigated whether horizontal load training incorporating lateral acceleration and deceleration would induce superior performance adaptations with respect to COD speed, compared with common vertically oriented maximal strength (squats and deadlifts), explosive strength (power clean and high pull), and vertical jumping exercises. Male U15 team sport athletes (n = 45) were assigned to 1 of 4 groups and performed 2 intervention training sessions per week for 4 weeks, in addition to their usual sport-specific training. Before and after the training period, COD speed, countermovement and drop jump heights, 1-legged lateral jump, and standing long jump performance were assessed. All 4 training groups improved COD speed (p ≤ 0.01, effect size [ES] ≥1.35). Countermovement and 1-legged lateral jump performance improved with the horizontal load (p < 0.01, ES = 0.81 and p < 0.01, ES = 1.36), maximal (p = 0.01, ES = 0.56 and p < 0.01, ES = 1.14), and explosive strength training (p < 0.01, ES = 0.95 and p < 0.01, ES = 1.60, respectively). The standing long jump improved with the maximal (p < 0.01, ES = 1.14) and explosive strength training (p < 0.01, ES = 0.60). In conclusion, all 4 training methods improved the COD speed in junior U15 team sport athletes. These findings emphasize the importance of well-developed lower-body strength and power, which contribute to fast COD speed. From a practical perspective, conditioning programs for junior athletes can incorporate horizontally and vertically oriented exercises with similar effectiveness on COD speed.

Selective Utilization of Benzimidazolyl-Norcobamides as Cofactors by the Tetrachloroethene Reductive Dehalogenase of Sulfurospirillum multivorans.

The organohalide-respiring bacterium Sulfurospirillum multivorans produces a unique cobamide, namely, norpseudo-B12, which serves as cofactor of the tetrachloroethene (PCE) reductive dehalogenase (PceA). As previously reported, a replacement of the adeninyl moiety, the lower base of the cofactor, by exogenously applied 5,6-dimethylbenzimidazole led to inactive PceA. To explore the general effect of benzimidazoles on the PCE metabolism, the susceptibility of the organism for guided biosynthesis of various singly substituted benzimidazolyl-norcobamides was investigated, and their use as cofactor by PceA was analyzed. Exogenously applied 5-methylbenzimidazole (5-MeBza), 5-hydroxybenzimidazole (5-OHBza), and 5-methoxybenzimidazole (5-OMeBza) were found to be efficiently incorporated as lower bases into norcobamides (NCbas). Structural analysis of the NCbas by nuclear magnetic resonance spectroscopy uncovered a regioselectivity in the utilization of these precursors for NCba biosynthesis. When 5-MeBza was added, a mixture of 5-MeBza-norcobamide and 6-MeBza-norcobamide was formed, and the PceA enzyme activity was affected. In the presence of 5-OHBza, almost exclusively 6-OHBza-norcobamide was produced, while in the presence of 5-OMeBza, predominantly 5-OMeBza-norcobamide was detected. Both NCbas were incorporated into PceA, and no negative effect on the PceA activity was observed. In crystal structures of PceA, both NCbas were bound in the base-off mode with the 6-OHBza and 5-OMeBza lower bases accommodated by the same solvent-exposed hydrophilic pocket that harbors the adenine as the lower base of authentic norpseudo-B12 In this study, a selective production of different norcobamide isomers containing singly substituted benzimidazoles as lower bases is shown, and unique structural insights into their utilization as cofactors by a cobamide-containing enzyme are provided.IMPORTANCE Guided biosynthesis of norcobamides containing singly substituted benzimidazoles as lower bases by the organohalide-respiring epsilonproteobacterium Sulfurospirillum multivorans is reported. An unprecedented specificity in the formation of norcobamide isomers containing hydroxylated or methoxylated benzimidazoles was observed that implicated a strict regioselectivity of the norcobamide biosynthesis in the organism. In contrast to 5,6-dimethylbenzimidazolyl-norcobamide, the incorporation of singly substituted benzimidazolyl-norcobamides as a cofactor into the tetrachloroethene reductive dehalogenase was not impaired. The enzyme was found to be functional with different isomers and not limited to the use of adeninyl-norcobamide. Structural analysis of the enzyme equipped with either adeninyl- or benzimidazolyl-norcobamide cofactors visualized for the first time structurally different cobamides bound in base-off conformation to the cofactor-binding site of a cobamide-containing enzyme.

The SMUL_1544 Gene Product Governs Norcobamide Biosynthesis in the Tetrachloroethene-Respiring Bacterium Sulfurospirillum multivorans.

UNLABELLED: The tetrachloroethene (PCE)-respiring bacterium Sulfurospirillum multivorans produces a unique cobamide, namely, norpseudo-B12, which, in comparison to other cobamides, e.g., cobalamin and pseudo-B12, lacks the methyl group in the linker moiety of the nucleotide loop. In this study, the protein SMUL_1544 was shown to be responsible for the formation of the unusual linker moiety, which is most probably derived from ethanolamine-phosphate (EA-P) as the precursor. The product of the SMUL_1544 gene successfully complemented a Salmonella enterica ΔcobD mutant. The cobD gene encodes an l-threonine-O-3-phosphate (l-Thr-P) decarboxylase responsible for the synthesis of (R)-1-aminopropan-2-ol O-2-phosphate (AP-P), required specifically for cobamide biosynthesis. When SMUL_1544 was produced in the heterologous host lacking CobD, norpseudo-B12 was formed, which pointed toward the formation of EA-P rather than AP-P. Guided cobamide biosynthesis experiments with minimal medium supplemented with l-Thr-P supported cobamide biosynthesis in S. enterica producing SMUL_1544 or S. multivorans Under these conditions, both microorganisms synthesized pseudo-B12 This observation indicated a flexibility in the SMUL_1544 substrate spectrum. From the formation of catalytically active PCE reductive dehalogenase (PceA) in S. multivorans cells producing pseudo-B12, a compatibility of the respiratory enzyme with the cofactor was deduced. This result might indicate a structural flexibility of PceA in cobamide binding. Feeding of l-[3-(13)C]serine to cultures of S. multivorans resulted in isotope labeling of the norpseudo-B12 linker moiety, which strongly supports the hypothesis of EA-P formation from l-serine-O-phosphate (l-Ser-P) in this organism. IMPORTANCE: The identification of the gene product SMUL_1544 as a putative l-Ser-P decarboxylase involved in norcobamide biosynthesis in S. multivorans adds a novel module to the assembly line of cobamides (complete corrinoids) in prokaryotes. Selected cobamide-containing enzymes (e.g., reductive dehalogenases) showed specificity for their cobamide cofactors. It has recently been proposed that the structure of the linker moiety of norpseudo-B12 and the mode of binding of the EA-P linker to the PceA enzyme reflect the high specificity of the enzyme for its cofactor. Data reported herein do not support this idea. In fact, norpseudo-B12 was functional in the cobamide-dependent methionine biosynthesis of S. enterica, raising questions about the role of norcobamides in nature.

Spin-adapted matrix product states and operators.

Matrix product states (MPSs) and matrix product operators (MPOs) allow an alternative formulation of the density matrix renormalization group algorithm introduced by White. Here, we describe how non-abelian spin symmetry can be exploited in MPSs and MPOs by virtue of the Wigner-Eckart theorem at the example of the spin-adapted quantum chemical Hamiltonian operator.

New Approaches for ab initio Calculations of Molecules with Strong Electron Correlation.

Reliable quantum chemical methods for the description of molecules with dense-lying frontier orbitals are needed in the context of many chemical compounds and reactions. Here, we review developments that led to our new computational toolbox which implements the quantum chemical density matrix renormalization group in a second-generation algorithm. We present an overview of the different components of this toolbox.

Orbital entanglement and CASSCF analysis of the Ru-NO bond in a Ruthenium nitrosyl complex.

Complete active space self-consistent field (CASSCF) wavefunctions and an orbital entanglement analysis obtained from a density-matrix renormalisation group (DMRG) calculation are used to understand the electronic structure, and, in particular, the Ru-NO bond of a Ru nitrosyl complex. Based on the configurations and orbital occupation numbers obtained for the CASSCF wavefunction and on the orbital entropy measurements evaluated for the DMRG wavefunction, we unravel electron correlation effects in the Ru coordination sphere of the complex. It is shown that Ru-NO π bonds show static and dynamic correlation, while other Ru-ligand bonds feature predominantly dynamic correlation. The presence of static correlation requires the use of multiconfigurational methods to describe the Ru-NO bond. Subsequently, the CASSCF wavefunction is analysed in terms of configuration state functions based on localised orbitals. The analysis of the wavefunctions in the electronic singlet ground state and the first triplet state provides a picture of the Ru-NO moiety beyond the standard representation based on formal oxidation states. A distinct description of the Ru and NO fragments is advocated. The electron configuration of Ru is an equally weighted superposition of Ru(II) and Ru(III) configurations, with the Ru(III) configuration originating from charge donation mostly from Cl ligands. However, and contrary to what is typically assumed, the electronic configuration of the NO ligand is best described as electroneutral.

An efficient matrix product operator representation of the quantum chemical Hamiltonian.

We describe how to efficiently construct the quantum chemical Hamiltonian operator in matrix product form. We present its implementation as a density matrix renormalization group (DMRG) algorithm for quantum chemical applications. Existing implementations of DMRG for quantum chemistry are based on the traditional formulation of the method, which was developed from the point of view of Hilbert space decimation and attained higher performance compared to straightforward implementations of matrix product based DMRG. The latter variationally optimizes a class of ansatz states known as matrix product states, where operators are correspondingly represented as matrix product operators (MPOs). The MPO construction scheme presented here eliminates the previous performance disadvantages while retaining the additional flexibility provided by a matrix product approach, for example, the specification of expectation values becomes an input parameter. In this way, MPOs for different symmetries - abelian and non-abelian - and different relativistic and non-relativistic models may be solved by an otherwise unmodified program.

Selection of active spaces for multiconfigurational wavefunctions.

The efficient and accurate description of the electronic structure of strongly correlated systems is still a largely unsolved problem. The usual procedures start with a multiconfigurational (usually a Complete Active Space, CAS) wavefunction which accounts for static correlation and add dynamical correlation by perturbation theory, configuration interaction, or coupled cluster expansion. This procedure requires the correct selection of the active space. Intuitive methods are unreliable for complex systems. The inexpensive black-box unrestricted natural orbital (UNO) criterion postulates that the Unrestricted Hartree-Fock (UHF) charge natural orbitals with fractional occupancy (e.g., between 0.02 and 1.98) constitute the active space. UNOs generally approximate the CAS orbitals so well that the orbital optimization in CAS Self-Consistent Field (CASSCF) may be omitted, resulting in the inexpensive UNO-CAS method. A rigorous testing of the UNO criterion requires comparison with approximate full configuration interaction wavefunctions. This became feasible with the advent of Density Matrix Renormalization Group (DMRG) methods which can approximate highly correlated wavefunctions at affordable cost. We have compared active orbital occupancies in UNO-CAS and CASSCF calculations with DMRG in a number of strongly correlated molecules: compounds of electronegative atoms (F2, ozone, and NO2), polyenes, aromatic molecules (naphthalene, azulene, anthracene, and nitrobenzene), radicals (phenoxy and benzyl), diradicals (o-, m-, and p-benzyne), and transition metal compounds (nickel-acetylene and Cr2). The UNO criterion works well in these cases. Other symmetry breaking solutions, with the possible exception of spatial symmetry, do not appear to be essential to generate the correct active space. In the case of multiple UHF solutions, the natural orbitals of the average UHF density should be used. The problems of the UNO criterion and their potential solutions are discussed: finding the UHF solutions, discontinuities on potential energy surfaces, and inclusion of dynamical electron correlation and generalization to excited states.

Self-consistent embedding of density-matrix renormalization group wavefunctions in a density functional environment.

We present the first implementation of a density matrix renormalization group algorithm embedded in an environment described by density functional theory. The frozen density embedding scheme is used with a freeze-and-thaw strategy for a self-consistent polarization of the orbital-optimized wavefunction and the environmental densities with respect to each other.

Exogenous 5,6-dimethylbenzimidazole caused production of a non-functional tetrachloroethene reductive dehalogenase in Sulfurospirillum multivorans.

Corrinoid-dependent reductive dehalogenation is mediated by phylogenetically diverse anaerobic bacteria that either synthesize corrinoids de novo or are dependent on corrinoid salvaging from the environment. The tetrachloroethene (PCE) reductive dehalogenase (PceA) of the Gram-negative Epsilonproteobacterium Sulfurospirillum multivorans harbours a norpseudo-B12 as corrinoid cofactor. Norpseudo-B12 differs from coenzyme B12 in the nucleotide loop structure. Adenine instead of 5,6-dimethylbenzimidazole (DMB) serves as lower ligand base of the central cobalt ion, and the nucleotide loop of norpseudo-B12 lacks a methyl group at position 176. In this study, S. multivorans was grown anaerobically with PCE in the presence of DMB. At a DMB concentration of 25 µM, the adenine moiety in the nucleotide loop of norpseudo-B12 was quantitatively replaced by DMB. The formation of the DMB-containing nor-B12 severely affected PCE-dependent growth and the PceA activity. In DMB-treated cells processing of the cytoplasmic PceA precursor was impeded, a result pointing to retarded cofactor incorporation. PceA enriched from cells cultivated with DMB contained nor-B12 . Nor-B12 purified from cells grown in the presence of DMB mediated the abiotic reductive dehalogenation of trichloroacetate to dichloroacetate at a 25-fold lower rate in comparison with norpseudo-B12 , a fact underpinning the relevance of norpseudo-B12 as efficient catalyst for reductive dehalogenation in general.

Combined C and Cl isotope effects indicate differences between corrinoids and enzyme (Sulfurospirillum multivorans PceA) in reductive dehalogenation of tetrachloroethene, but not trichloroethene.

The role of the corrinoid cofactor in reductive dehalogenation catalysis by tetrachloroethene reductive dehalogenase (PceA) of Sulfurospirillum multivorans was investigated using isotope analysis of carbon and chlorine. Crude extracts containing PceA--harboring either a native norpseudo-B12 or the alternative nor-B12 cofactor--were applied for dehalogenation of tetrachloroethene (PCE) or trichloroethene (TCE), and compared to abiotic dehalogenation with the respective purified corrinoids (norpseudovitamin B12 and norvitamin B12), as well as several commercially available cobalamins and cobinamide. Dehalogenation of TCE resulted in a similar extent of C and Cl isotope fractionation, and in similar dual-element isotope slopes (εC/εCl) of 5.0-5.3 for PceA enzyme and 3.7-4.5 for the corrinoids. Both observations support an identical reaction mechanism. For PCE, in contrast, observed C and Cl isotope fractionation was smaller in enzymatic dehalogenation, and dual-element isotope slopes (2.2-2.8) were distinctly different compared to dehalogenation mediated by corrinoids (4.6-7.0). Remarkably, εC/εCl of PCE depended in addition on the corrinoid type: εC/εCl values of 4.6 and 5.0 for vitamin B12 and norvitamin B12 were significantly different compared to values of 6.9 and 7.0 for norpseudovitamin B12 and dicyanocobinamide. Our results therefore suggest mechanistic and/or kinetic differences in catalytic PCE dehalogenation by enzymes and different corrinoids, whereas such differences were not observed for TCE.

Determining factors for the accuracy of DMRG in chemistry.

The Density Matrix Renormalization Group (DMRG) algorithm has been a rising star for the accurate ab initio exploration of Born-Oppenheimer potential energy surfaces in theoretical chemistry. However, owing to its iterative numerical nature, pitfalls that can affect the accuracy of DMRG energies need to be circumvented. Here, after a brief introduction into this quantum chemical method, we discuss criteria that determine the accuracy of DMRG calculations.