Concurrent Cross Metathesis and Enzymatic Oxidation: Enabling Off-Equilibrium Transformations

Criss‐cross catalysis: H. Zhao, J. F. Hartwig and co‐workers have combined homogeneous alkene metathesis and biocatalysis in a concurrent fashion. A ruthenium–N‐heterocyclic carbene (NHC) complex provides an equilibrating mixture of cross metathesis products. The selective simultaneous epoxidation by cytochrome P450 BM3 enables product yields well above the hypothetical two‐step process

On the nature of amorphous polymorphism of water

We report elastic and inelastic neutron scattering experiments on different amorphous ice modifications. It is shown that an amorphous structure (HDA') indiscernible from the high-density phase (HDA), obtained by compression of crystalline ice, can be formed from the very high-density phase (vHDA) as an intermediate stage of the transition of vHDA into its low-density modification (LDA'). Both, HDA and HDA' exhibit comparable small angle scattering signals characterizing them as structures heterogeneous on a length scale of a few nano-meters. The homogeneous structures are the initial and final transition stages vHDA and LDA', respectively. Despite, their apparent structural identity on a local scale HDA and HDA' differ in their transition kinetics explored by in situ experiments. The activation energy of the vHDA-to-LDA' transition is at least 20 kJ/mol higher than the activation energy of the HDA-to-LDA transition

Capturing conformational states in proteins using sparse paramagnetic NMR data

Capturing conformational changes in proteins or protein-protein complexes is a challenge for both experimentalists and computational biologists. Solution nuclear magnetic resonance (NMR) is unique in that it permits structural studies of proteins under greatly varying conditions, and thus allows us to monitor induced structural changes. Paramagnetic effects are increasingly used to study protein structures as they give ready access to rich structural information of orientation and long-range distance restraints from the NMR signals of backbone amides, and reliable methods have become available to tag proteins with paramagnetic metal ions site-specifically and at multiple sites. In this study, we show how sparse pseudocontact shift (PCS) data can be used to computationally model conformational states in a protein system, by first identifying core structural elements that are not affected by the environmental change, and then computationally completing the remaining structure based on experimental restraints from PCS. The approach is demonstrated on a 27 kDa two-domain NS2B-NS3 protease system of the dengue virus serotype 2, for which distinct closed and open conformational states have been observed in crystal structures. By changing the input PCS data, the observed conformational states in the dengue virus protease are reproduced without modifying the computational procedure. This data driven Rosetta protocol enables identification of conformational states of a protein system, which are otherwise difficult to obtain either experimentally or computationally.This study was supported by the Australian Research Council (DP120100561, DP150100383), which the authors gratefully acknowledge

Fitness Impact of Obligate Intranuclear Bacterial Symbionts Depends on Host Growth Phase

According to text book definition, parasites reduce the fitness of their hosts whereas mutualists provide benefits. But biotic and abiotic factors influence symbiotic interactions, thus under certain circumstances parasites can provide benefits and mutualists can harm their host. Here we addressed the question which intrinsic biotic factors shape a symbiosis and are crucial for the outcome of the interaction between the obligate intranuclear bacterium Holospora caryophila (Alphaproteobacteria; Rickettsiales) and its unicellular eukaryotic host Paramecium biaurelia (Alveolata; Ciliophora). The virulence of H. caryophila, i.e., the negative fitness effect on host division and cell number, was determined by growth assays of several P. biaurelia strains. The performances of genetically identical lines either infected with H. caryophila or symbiont-free were compared. Following factors were considered as potentially influencing the outcome of the interaction: (1) host strain, (2) parasite strain, and (3) growth phases of the host. All three factors revealed a strong effect on the symbiosis. In presence of H. caryophila, the Paramecium density in the stationary growth phase decreased. Conversely, a positive effect of the bacteria during the exponential phase was observed for several host × parasite combinations resulting in an increased growth rate of infected P. biaurelia. Furthermore, the fitness impact of the tested endosymbionts on different P. biaurelia lines was not only dependent on one of the two involved strains but distinct for the specific combination. Depending on the current host growth phase, the presence of H. caryophila can be harmful or advantageous for P. biaurelia. Thus, under the tested experimental conditions, the symbionts can switch from the provision of benefits to the exploitation of host resources within the same host population and a time-span of less than 6 days

Rewriting History: Repurposing Domain-Specific CGRAs

Coarse-grained reconfigurable arrays (CGRAs) are domain-specific devices promising both the flexibility of FPGAs and the performance of ASICs. However, with restricted domains comes a danger: designing chips that cannot accelerate enough current and future software to justify the hardware cost. We introduce FlexC, the first flexible CGRA compiler, which allows CGRAs to be adapted to operations they do not natively support. FlexC uses dataflow rewriting, replacing unsupported regions of code with equivalent operations that are supported by the CGRA. We use equality saturation, a technique enabling efficient exploration of a large space of rewrite rules, to effectively search through the program-space for supported programs. We applied FlexC to over 2,000 loop kernels, compiling to four different research CGRAs and 300 generated CGRAs and demonstrate a 2.2$\times$ increase in the number of loop kernels accelerated leading to 3$\times$ speedup compared to an Arm A5 CPU on kernels that would otherwise be unsupported by the accelerator