Helical Propensity in an Intrinsically Disordered Protein Accelerates Ligand Binding

Many intrinsically disordered proteins fold upon binding to other macromolecules. The secondary structure present in the well‐ordered complex is often formed transiently in the unbound state. The consequence of such transient structure for the binding process is, however, not clear. The activation domain of the activator for thyroid hormone and retinoid receptors (ACTR) is intrinsically disordered and folds upon binding to the nuclear coactivator binding domain (NCBD) of the CREB binding protein. A number of mutants was designed that selectively perturbs the amount of secondary structure in unbound ACTR without interfering with the intermolecular interactions between ACTR and NCBD. Using NMR spectroscopy and fluorescence‐monitored stopped‐flow kinetic measurements we show that the secondary structure content in helix 1 of ACTR indeed influences the binding kinetics. The results thus support the notion of preformed secondary structure as an important determinant for molecular recognition in intrinsically disordered proteins.     

A note on the dynamical zeta function of general toral endomorphisms

It is well-known that the Artin-Mazur dynamical zeta function of a hyperbolic or quasi-hyperbolic toral automorphism is a rational function, which can be calculated in terms of the eigenvalues of the corresponding integer matrix. We give an elementary proof of this fact that extends to the case of general toral endomorphisms without change. The result is a closed formula that can be calculated by integer arithmetic only. We also address the functional equation and the relation between the Artin-Mazur and Lefschetz zeta functions.     

In vitro and in vivo biocompatibility study on laser 3D microstructurable polymers

Films and microstructured scaffolds have been fabricated using direct laser writing out of different polymers: hybrid organic-inorganic ORMOCORE b59, acrylate-based AKRE23, novel organic-inorganic Zr containing hybrid SZ2080, and biodegradable PEG-DA-258. Adult myogenic stem cells were grown on these surfaces in vitro. Their adhesion, growth, and viability test results suggest good potential applicability of the materials in biomedical practice. Pieces of these polymers were implanted in rat’s paravertebral back tissue. Histological examination of the implants and surrounding tissue ex vivo after 3 weeks of implantation was conducted and results show the materials to be at least as biocompatible as surgical clips or sutures. The applied direct laser writing technique seems to offer good future prospects in a polymeric 3D scaffold design for artificial tissue engineering with autologous stem cells.     

Unicity of Types for Supercuspidal Representations of GLN

Let F be a non-Archimedean local field, with the ring of integerso_F. Let G = GL_N(F), K = GL_N (o_F), and be a supercuspidal representationof G. We show that there exists a unique irreducible smoothrepresentation of K, such that the restriction to K of a smoothirreducible representation ' of G contains if and only if 'is isomorphic to ° det, where is an unramified quasicharacterof F^x. Moreover, we show that contains with the multiplicity1. As a corollary we obtain a kind of inertial local Langlandscorrespondence. 2000 Mathematics Subject Classification 22E50.     

PICOSECOND ABSORPTION STUDIES OF Zn-OCTAETHYLPORPHIN π-MONOANIONS

Abstract— Using the example of Zn-octaethylporphin π-monoanion solution in tetrahydrofuran, we studied the dynamics of ultrafast photoprocesses in porphyrin π-anions using a tunable picosecond absorption spectrometer. The deactivation kinetics of the lowest excited electronic (doublet) state of Zn-octaethylporphin iT-monoanion has been determined and was found to be followed by a single exponential function with the characteristic time 135 ps. It is shown that upon picosecond excitation to the long wavelength absorption band (λ_max= 830 nm) the process of two-quantum photoionization of the involved monoanion is easily realized, with the results that the observable kinetics of spectral changes exhibit a strong dependence on the excitation intensity.     

Synthesis and Antibacterial Activity of New Azole,Diazole and Triazole Derivatives Based on p-Aminobenzoic Acid

The p-aminobenzoic acid was applied for the synthesis of substituted 1-phenyl-5-oxopyrrolidine derivatives containing benzimidazole, azole, oxadiazole, triazole, dihydrazone, and dithiosemicarbazide moieties in the structure. All the obtained compounds were evaluated for their in vitro antimicrobial activity against Staphylococcus aureus, Bacillus cereus, Listeria monocytogenes, Salmonella enteritidis, Escherichia coli, and Pseudomonas aeruginosa by using MIC and MBC assays. This study showed a good bactericidal activity of γ-amino acid and benzimidazoles derivatives. The antimicrobial activity of the most promising compounds was higher than ampicillin. Furthermore, two benzimidazoles demonstrated good antimicrobial activity against L. monocytogenes (MIC 15.62 µg/mL) that was four times more potent than ampicillin (MIC 65 µg/mL). Further studies are needed to better understand the mechanism of the antimicrobial activity as well as to generate antimicrobial compounds based on the 1-phenyl-5-oxopyrrolidine scaffold.     

pmx: Automated protein structure and topology generation for alchemical perturbations

Computational protein design requires methods to accurately estimate free energy changes in protein stability or binding upon an amino acid mutation. From the different approaches available, molecular dynamics‐based alchemical free energy calculations are unique in their accuracy and solid theoretical basis. The challenge in using these methods lies in the need to generate hybrid structures and topologies representing two physical states of a system. A custom made hybrid topology may prove useful for a particular mutation of interest, however, a high throughput mutation analysis calls for a more general approach. In this work, we present an automated procedure to generate hybrid structures and topologies for the amino acid mutations in all commonly used force fields. The described software is compatible with the Gromacs simulation package. The mutation libraries are readily supported for five force fields, namely Amber99SB, Amber99SB*‐ILDN, OPLS‐AA/L, Charmm22*, and Charmm36. © 2014 The Authors Journal of Computational Chemistry Published by Wiley Periodicals, Inc.     

CP MAS Kinetics Study of Ionic Liquids Confined in Mesoporous Silica: Convergence of Non-Classical and Classical Spin Coupling Models

The high data point density measurements of ¹H→¹¹B cross-polarization (CP) kinetics upon magic-angle spinning (MAS) of [bmim][BF₄] confined in mesoporous SBA-15 and MCM-41 were carried out. The complex shaped ¹¹B CP MAS signals were observed in both silica and decomposed into two Lorentz components. This points towards the possibility of bimodal distribution of [bmim][BF₄] in the studied confinements. The convergence of classical and non-classical spin coupling models was deduced processing CP kinetic curves. A good fit of the theoretical curves to the experimental data was achieved using both models without any non-random deviations between theory and experiment to appear. The convergence of spin coupling models was discussed in terms of relatively high mobility of BF₄ ^? anion respect to the cation and the dynamics of anions in pores. These factors delete the borders between spin clusters. The spin diffusion along the pore surfaces in MCM-41 is more than twice faster than in SBA-15.