Parallel biomolecular computation on surfaces with advanced finite automata

A biomolecular, programmable 3-symbol-3-state finite automaton is reported. This automaton computes autonomously with all of its components, including hardware, software, input, and output being biomolecules mixed together in solution. The hardware consisted of two enzymes: an endonuclease, BbvI, and T4 DNA ligase. The software (transition rules represented by transition molecules) and the input were double-stranded (ds) DNA oligomers. Computation was carried out by autonomous processing of the input molecules via repetitive cycles of restriction, hybridization, and ligation reactions to produce a final-state output in the form of a dsDNA molecule. The 3-symbol-3-state deterministic automaton is an extension of the 2-symbol-2-state automaton previously reported, and theoretically it can be further expanded to a 37-symbol-3-state automaton. The applicability of this design was further amplified by employing surface-anchored input molecules, using the surface plasmon resonance technology to monitor the computation steps in real time. Computation was performed by alternating the feed solutions between endonuclease and a solution containing the ligase, ATP, and appropriate transition molecules. The output detection involved final ligation with one of three soluble detection molecules. Parallel computation and stepwise detection were carried out automatically with a Biacore chip that was loaded with four different inputs.     

Pharmacophore modeling, 3D-QSAR,docking, and molecular dynamics simulation on topoisomerase IV inhibitors of wild type Staphylococcus aureus

Staphylococcus aureus is a gram-positive bacterium. It is a foremost cause of skin and respiratory infections, endocarditis, osteomyelitis, Ritter’s disease, and bacteraemia. Topoisomerase enzyme is involved in preventing or correcting topological problems of overwinding or underwinding occurring in DNA before replication process. An exhaustive molecular modeling studies that includes pharmacophore modeling, ligand-based three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking, molecular dynamics simulation, and ADME calculations were performed on isothiazoloquinolones derivatives which are reported as effective inhibitors against topoisomerase IV of wild type S. aureus. In pharmacophore modeling by using pharmacophore alignment and scoring engine (PHASE) a five-point model (AHHRR.3) was generated with existing compounds having statistical significant as correlation coefficient (R ² = 0.954), cross-validation coefficient (Q ² = 0.650), and F value of 130.5. Ligand-based 3D-QSAR study was applied using comparative molecular field analysis (CoMFA) with Q ² = 0.616, R ² = 0.989, and comparative molecular similarity indices analysis (CoMSIA) with Q ² = 0.510, R ² = 0.995. The predictive ability of this model was determined using a test set of molecules that gave acceptable predictive correlation (R ² Pred) values 0.55 and 0.56 for CoMFA and CoMSIA, respectively. Docking and molecular dynamic simulations were employed to position the inhibitors into protein active site to find out the most probable binding mode and most reliable conformations. Developed pharmacophore models and docking methods provide guidance to design enhanced activity molecules.

     

Triple B≡B bond: from a perfect Lewis structure to a dominant π-back-donation. The need for a reference point

Abstract

Coordination of a B₂ fragment by two σ-donor ligands could lead to complexes with a formal triple B≡B bond L→B≡B←L. Formation of L-B σ-bond leads to excess electrons around the B₂ central fragment. A subsequent direct π-charge transfer from B≡B moiety to the ligands L is a necessary condition for incorporation of BB fragment to the conjugated LBBL system. Quantum-chemical calculations (DFT, CCD, and CAS) show that the stabilization of a linear L-BB-L structure is possible but is accompanied by lowering of the B-B bond order. The ammonia-boryne structure H3N→BB←NH₃, which is studied as a model system, shows a perfect triple BB fragment relative to other LBBL adducts. The comparison of the conjugation between the B₂ fragment and two types of σ-donor ligands, with or without π-back-donation, provides an indication of the character of BB multiple bond. Three studied boryne molecules are calculated to have a high barrier for dissociation XXBBXX→XX?+?BBXX, yet a high reactivity of these compounds is indicated by the low-lying excited states of borynes (ΔE_S0-S1<1.5?eV). The largest gap ΔE_S0-S1～2.6?eV is calculated for the room temperature stable bis-NHC-boryne.     

Homology modelling and virtual screening to explore potent inhibitors for MAP2K3 protein

Structural Chemistry - MAP2K3 protein is mitogen-activated protein kinase belonging to the family of kinases involved in intracellular cell proliferation. The mammalian MAPK family that consists of...     

On‐axis shaping of second‐harmonic beams

We report complete spatial shaping (both phase and amplitude) of the second‐harmonic beam generated in a nonlinear photonic crystal. Using a collinear second‐order process in a nonlinear computer generated hologram imprinted on the crystal, the desired beam is generated on‐axis and in the near field. This enables compact and efficient one‐dimensional beam shaping in comparison to previously demonstrated off‐axis Fourier holograms. We experimentally demonstrate the second‐harmonic generation of high‐order Hermite–Gauss, top hats and arbitrary skyline‐shaped beams.

     

A Stationary Phase Approach to the Weak Coupling Schrödinger Equation

We study the dynamics of a quantum particle governed by a linear Schrödinger equation with a scaled Gaussian potential. In the weak coupling limit the average dynamics of such a particle can be described by a linear Boltzmann equation. In this work we prove a bound for the rate at which the average dynamics of the quantum particle approach linear Boltzmann equation dynamics. For the so called simple diagrams, we use a stationary phase approach to establish an asymptotic expansion that provides the bound. Our stationary phase approach also provides a simple, formal method for computing the Boltzmann limit. Our work uses and extends results developed by L. Erdös and H.T. Yau.     

Immobilization of chiral oxazaborolidine catalyst over highly ordered 3D mesoporous silica with Ia3d symmetry for enantioselective reduction of prochiral ketone

Here we demonstrate for the first time the encapsulation of a chiral oxazaborolidine complex in the 3D mesoporous channels of an amine functionalized KIT-6 material via covalent bonding through a post-synthetic approach. The physico-chemical properties of the pure and immobilized KIT-6 catalysts were obtained by various techniques such as XRD, nitrogen adsorption, HRSEM, UV-Vis diffuse reflectance spectroscopy, and FT-IR spectroscopy. It has been found that the structural stability of the KIT-6 was not affected even after the immobilization of a significant amount of chiral ligand inside the mesoporous channels of the support. However, the values of structural parameters such as the specific surface area and the specific pore volume of the KIT-6 support was significantly lower than the pure KIT-6 support. The chemical interaction between the chiral ligand inside the mesochannels and the KIT-6 support was also confirmed by UV-Vis and FT-IR spectroscopy. The chiral catalytic performance of the immobilized catalysts for the enantioselective reduction of aromatic prochiral ketones was demonstrated and the results were compared with chiral catalyst immobilized supports with uni-dimensional porous structures, such as MCM-41 and SBA-15. Among the catalysts studied, chiral catalyst immobilized KIT-6 showed the highest performance with a high product yield and a high enantioselectivity due to its 3D porous structure with two continuous and interpenetrating systems of chiral channels and an interwoven 3D cylindrical type pores of Ia3d symmetry. The catalyst also exhibited much better recycling capability than other chiral catalyst supported mesoporous materials used in the study.