Simulation of multiphase systems utilizing independent force fields to control intraphase and interphase behavior

Fixed‐charge empirical force fields have been developed and widely used over the past three decades for all‐atom molecular simulations. Most simulation programs providing these methods enable only one set of force field parameters to be used for the entire system. Whereas this is generally suitable for single‐phase systems, the molecular environment at the interface between two phases may be sufficiently different from the individual phases to require a different set of parameters to be used to accurately represent the system. Recently published simulations of peptide adsorption to material surfaces using the CHARMM force field have clearly demonstrated this issue by revealing that calculated values of adsorption free energy substantially differ from experimental results. Whereas nonbonded parameters could be adjusted to correct this problem, this cannot be done without also altering the conformational behavior of the peptide in solution, for which CHARMM has been carefully tuned. We have developed a dual‐force‐field approach (Dual‐FF) to address this problem and implemented it in the CHARMM simulation package. This Dual‐FF method provides the capability to use two separate sets of nonbonded force field parameters within the same simulation: one set to represent intraphase interactions and a separate set to represent interphase interactions. Using this approach, we show that interfacial parameters can be adjusted to correct errors in peptide adsorption free energy without altering peptide conformational behavior in solution. This program thus provides the capability to enable both intraphase and interphase molecular behavior to be accurately and efficiently modeled in the same simulation. © 2012 Wiley Periodicals, Inc.     

Matrix isolation infrared observation of N3 using a nitrogen microwave discharge plasma source

The asymmetric stretching band of the N₃ radical in a nitrogen matrix at 1657.5?cm^?1 has been observed by directing the output of a nitrogen microwave discharge plasma source onto a CsI window at 12?K. The identification and assignment of this band to the N₃ radical has been accomplished by performing isotopic experiments, matrix annealing experiments, and photolysis experiments. The observed N₃ band positions are compared to literature frequencies observed in matrix isolation experiments using other generation sources and to literature theoretical frequencies calculated using high level ab initio and density functional theory methods. Temperature-dependent deposition experiments (10–20?K) and additional isotopic discharge plus co-deposition experiments are also performed in an effort to determine if the N₃ radical is being formed in the gas phase or by matrix surface reactions, and in order to gain insight into the reaction mechanism. After considering all of the mechanistic evidence (temperature-dependent and isotopic discharge/co-deposition spectra, theoretical reaction energetics, gas phase reaction kinetics, isotopic N₃ distributions), it is concluded that the N₃ radicals are being formed from the reaction of N(²D) atoms with vibrationally excited N₂ molecules in the nitrogen matrix via a linear (end-on) pathway.     

Direct formation of hydrogen peroxide from H2/O2 using a gold catalyst

Supported Au catalysts are very selective for the direct formation of hydrogen peroxide from H2/O2 mixtures at 2 degrees C; the rate of H2O2 synthesis is markedly increased if Au-Pd alloy nanoparticles are generated by the addition of Pd.     

Active-site coating for molecular discrimination in heterogeneous catalysis

A coherent layer of zeolite A has been applied to a SiO2-supported Pt-Fe oxidation catalyst, using total surface charge-reversal. The zeolite has tracked the metals into the pore structure of the support, covering the active sites. The zeolite channel size is large enough to allow access of CO and O2 to the active sites, and to allow CO2 to emerge, but it excludes larger molecules. The presence of the zeolite membrane transforms the supported Pt-Fe into a highly specific catalyst, which can discriminate between CO and butane, even after the macroscopic catalyst particles are crushed.     

Synthesis of Vibegron Enabled by a Ketoreductase Rationally Designed for High pH Dynamic Kinetic Reduction

Described here is an efficient stereoselective synthesis of vibegron enabled by an enzymatic dynamic kinetic reduction that proceeds in a high‐pH environment. To overcome enzyme performance limitations under these conditions, a ketoreductase was evolved by a computationally and structurally aided strategy to increase cofactor stability through tighter binding.     

Heteroatom derivatives of indene: V. Vibrational spectra of benzimidazole

Infrared and Raman measurements for benzimidazole are presented and discussed, including its argon-matrix infrared spectrum. To assist in the assignment, benzimidazole's harmonic force fields for the 321G* and 631G* levels were scaled by scaled factors derived by fitting the respective computed force fields of other indene derivatives to previously reported experimental vibrational frequencies. Comparison to the best set of experimental wavenumbers, usually taken from the matrix, shows mean 321G* and 631G* deviations of 7.0 and 5.8 cm⁻¹ for the planar modes, and 14.0 and 6.8 cm⁻¹ for the nonplanar modes, respectively, with much of the error residing in imino-hydrogen group modes. Standard entropies are derived with the matrix wavenumbers and the methods of statistical mechanics. An attempt to determine standard entropies by calorimetric methods was unsuccessful. The triple-point temperature T_tp and enthalpy of fusion Δ¹_crH_m only are reported.     

Structure-activity relationships in purine-based inhibitor binding to HSP90 isoforms.

Inhibition of the ATPase activity of the chaperone protein HSP90 is a potential strategy for treatment of cancers. We have determined structures of the HSP90alpha N-terminal domain complexed with the purine-based inhibitor, PU3, and analogs with enhanced potency both in enzyme and cell-based assays. The compounds induce upregulation of HSP70 and downregulation of the known HSP90 client proteins Raf-1, CDK4, and ErbB2, confirming that the molecules inhibit cell growth by a mechanism dependent on HSP90 inhibition. We have also determined the first structure of the N-terminal domain of HSP90beta, complexed with PU3. The structures allow a detailed rationale to be developed for the observed affinity of the PU3 class of compounds for HSP90 and also provide a structural framework for design of compounds with improved binding affinity and drug-like properties.     

Microchip micellar electrokinetic chromatography coupled with electrochemical detection for analysis of synthetic oestrogen mimicking compounds

A miniaturised analytical system for separating and detecting a range of steroidal oestrogens, based on the coupling of a micromachined capillary electrophoresis chip with glassy-carbon electrode amperometric detector, is described. Factors influencing the on-chip separation utilising the technique micellar electrokinetic chromatography (MEKC) and detection processes are optimised. The addition of modifiers such as organic solvents and surfactants improve separation and resolution of these hydrophobic compounds. Using a borate running buffer (5 mM, pH 11) with 20% methanol and SDS (20 mM) and a separation voltage of 2000 V, baseline resolution is observed for 16-keto-17β-oestradiol, oestriol, 11β-hydroxyoestradiol, oestrone, and β-oestradiol in 420 s with limits of detection 16–84 μM. The implications for on-site environmental analysis are discussed.     

THE STRUCTURE OF PHYCOBILISOMES IN MUTANTS OF Synechococcus sp. STRAIN PCC 7942 DEVOID OF SPECIFIC LINKER POLYPEPTIDES

Abstract— The effect of elimination of the 30, 33 and 9 kDa phycobilisome rod-linker polypeptides on rod length was examined by electron microscopy of phycobilisomes isolated from wild-type Synechococcus sp. strain PCC 7942 and from genetically engineered mutants with lesions in the genes encoding the rod-linker polypeptides. The maximum rod length in the absence of the 33 kDa linker polypeptide was two phycocyanin hexamers, whereas rods with up to five hexamers were found in the mutant strain lacking the 30 kDa linker polypeptide. Elimination of the 9 kDa linker polypeptide did not have a significant effect on rod length. Finally, mutants lacking either the 30 or 33 kDa rod-associated linker polypeptides had an increased number of rods that terminated with a phycocyanin trimer. These observations are discussed with respect to the role of the linker polypeptides in the biosynthesis of the rod substructure.