New faster CHARMM molecular dynamics engine

We introduce a new faster molecular dynamics (MD) engine into the CHARMM software package. The new MD engine is faster both in serial (i.e., single CPU core) and parallel execution. Serial performance is approximately two times higher than in the previous version of CHARMM. The newly programmed parallelization method allows the MD engine to parallelize up to hundreds of CPU cores. © 2013 Wiley Periodicals, Inc.     

Characterization of the alnumycin gene cluster reveals unusual gene products for pyran ring formation and dioxan biosynthesis

Alnumycin is closely related to the benzoisochromanequinone (BIQ) polyketides such as actinorhodin. Exceptional structural features include differences in aglycone tailoring that result in the unique alnumycin chromophore and the existence of an unusual 4-hydroxymethyl-5-hydroxy-1,3-dioxan moiety. Cloning and sequencing of the alnumycin gene cluster from Streptomyces sp. CM020 revealed expected biosynthesis genes for polyketide assembly, but several genes encoding subsequent tailoring enzymes were highly atypical. Heterologous expression studies confirmed that all of the genes required for alnumycin biosynthesis resided within the sequenced clone. Inactivation of genes aln4 and aln5 showed that the mechanism of pyran ring formation differs from actinorhodin and granaticin pathways. Further inactivation studies identified two genes, alnA and alnB, involved in the synthesis and attachment of the dioxan moiety, and resulted in the production of the polyketide prealnumycin.     

Coupled-cluster theory in a projected atomic orbital basis

We present a biorthogonal formulation of coupled-cluster (CC) theory using a redundant projected atomic orbital (PAO) basis. The biorthogonal formulation provides simple equations, where the projectors involved in the definition of the PAO basis are absorbed in the integrals. Explicit expressions for the coupled-cluster singles and doubles equations are derived in the PAO basis. The PAO CC equations can be written in a form identical to the standard molecular orbital CC equations, only with integrals that are related to the atomic orbital integrals through different transformation matrices. The dependence of cluster amplitudes, integrals, and correlation energy contributions on the distance between the participating atomic centers and on the number of involved atomic centers is illustrated in numerical case studies. It is also discussed how the present reformulation of the CC equations opens new possibilities for reducing the number of involved parameters and thereby the computational cost.     

Stability and Photoisomerization of Stilbenes Isolated from the Bark of Norway Spruce Roots

Stilbenes or stilbenoids, major polyphenolic compounds of the bark of Norway spruce (Picea abies L. Karst), have potential future applications as drugs, preservatives and other functional ingredients due to their antioxidative, antibacterial and antifungal properties. Stilbenes are photosensitive and UV and fluorescent light induce trans to cis isomerisation via intramolecular cyclization. So far, the characterizations of possible new compounds derived from trans-stilbenes under UV light exposure have been mainly tentative based only on UV or MS spectra without utilizing more detailed structural spectroscopy techniques such as NMR. The objective of this work was to study the stability of biologically interesting and readily available stilbenes such as astringin and isorhapontin and their aglucones piceatannol and isorhapontigenin, which have not been studied previously. The effects of fluorescent and UV light and storage on the stability of trans stilbenes were assessed and the identification and characterisation of new compounds formed during our experiments were carried out by chromatographic (HPLC, GC) and spectroscopic techniques (UV, MS, NMR). The stilbenes undergo a trans to cis isomerisation under extended UV irradiation by intramolecular cyclisation (by the formation of a new C-C bond and the loss of two hydrogens) to phenanthrene structures. The characterised compounds are novel and not described previously.     

On solvability of a two-sided singular control problem

We study a two-sided singular control problem in a general linear diffusion setting and provide a set of conditions under which an optimal control exists uniquely and is of singular control type. Moreover, under these conditions the associated value function can be written in a quasi-explicit form. Furthermore, we investigate comparative static properties of the solution with respect to the volatility and control parameters. Lastly we illustrate the results with two explicit examples.     

Combined drug screening and confirmation by liquid chromatography time-of-flight mass spectrometry with reverse database search

A method based on in-source collision-induced dissociation (ISCID) liquid chromatography time-of-flight mass spectrometry (LC-TOFMS) and reverse target database search was developed and evaluated for drug screening and confirmation in analytical toxicology context. An established LC-TOFMS screening method, in which identification relies solely on protonated molecule accurate mass measurement, isotopic pattern fit, and retention time (RT), was completed to include 1–3 qualifier ions for each analyte in the database. The qualifier ions for 431 compounds were selected from the experimental ISCID spectra, and their molecular formulae were assigned by applying SmartFormula3D and MSFragmenter software. Three qualifier ions were assigned for 64.5%, two or three for 81.4%, one for 14.8%, and none for 3.7% of the compounds studied. Comparison between ISCID LC-TOFMS and LC-TOFMS with 25 authentic autopsy urine samples showed an improved confidence level with the ISCID method, as isomeric interferences were excluded in most cases. However, some false negative (FN) results were obtained at low concentration levels close to the reporting criteria. The cut-off concentration of the ISCID method was 10–100 ng/mL with 80% of the 49 representative compounds tested, and the level was approximately two times higher than that obtained by LC ion trap MS. The presented method enables simultaneous screening and confirmation whenever at least one qualifier ion is available, as applying an accurate mass precursor ion and one product ion surpasses the standard of four identification points that is required by the current EU protocol.     

A simple multichromophore design for energy transfer in distyrylbenzenes with pyrene pendants

A set of Don --> Acc <-- Don multichromophores was synthesized based on a simple design with two pyrene donors (absorbing antennae) connected to a bis-1,4-(3,4,5-trimethoxystyryl)benzene core acceptor using various flexible, nonconjugated tethers. Excitation of the pyrene donors at 276 nm in solution yields near exclusive emission from the core chromophore at 445-450 nm, with energy transfer efficiencies up to 92%, far better than achieved with simple mixtures. The simple tethering design imposes a high "local" concentration of the pyrene near the acceptor core unit that is maintained even at very low multichromophore concentrations. Solvent effects on absorption and emission spectra are very small, except in cases where a pi-conjugating O-C=O moiety of the tethering group is directly attached to the core chromophore, rather than being placed in the middle of the tether. Energy transfer in the systems is effective due to good donor-acceptor energy matching. The optimal energy transfer efficiency was achieved using an eight-atom flexible linker.     

Ends of metric measure spaces and Sobolev inequalities

Generalizing work of Li and Wang, we prove sharp volume growth/decay rates for ends of metric measure spaces supporting a (p,p)-Sobolev inequality. A sharp result for (q,p)-Sobolev inequalities is also proved. The first author was partially supported by Enterprise Ireland.     

Cu(I)-catalyzed reductive aldol cyclizations: diastereo- and enantioselective synthesis of beta-hydroxylactones

[reaction: see text] Copper bisphosphine complexes catalyze the intramolecular reductive aldol reaction of alpha,beta-unsaturated esters with ketones, affording five- and six-membered beta-hydroxylactones in high stereoselectivities. Utilization of chiral nonracemic bisphosphines render the cyclizations enantioselective.