Hydrophobic core flexibility modulates enzyme activity in HIV-1 protease

Human immunodeficiency virus Type-1 (HIV-1) protease is crucial for viral maturation and infectivity. Studies of protease dynamics suggest that the rearrangement of the hydrophobic core is essential for enzyme activity. Many mutations in the hydrophobic core are also associated with drug resistance and may modulate the core flexibility. To test the role of flexibility in protease activity, pairs of cysteines were introduced at the interfaces of flexible regions remote from the active site. Disulfide bond formation was confirmed by crystal structures and by alkylation of free cysteines and mass spectrometry. Oxidized and reduced crystal structures of these variants show the overall structure of the protease is retained. However, cross-linking the cysteines led to drastic loss in enzyme activity, which was regained upon reducing the disulfide cross-links. Molecular dynamics simulations showed that altered dynamics propagated throughout the enzyme from the engineered disulfide. Thus, altered flexibility within the hydrophobic core can modulate HIV-1 protease activity, supporting the hypothesis that drug resistant mutations distal from the active site can alter the balance between substrate turnover and inhibitor binding by modulating enzyme activity.     

Convenient and simple synthesis of 2-aminothiazoles by the reaction of α-halo ketone carbonyls with ammonium thiocyanate in the presence of N-methylimidazole

Substituted 2-aminothiazole derivatives were obtained as a result of N-methylimidazole catalyzed cyclization of α-halo ketone carbonyls with ammonium thiocyanate in water-alcoholic media. The generality of the method has been demonstrated by screening a series of aromatic/heteroaromatic/aliphatic α-halo ketones, α-halo β-diketones, and α-halo β-ketoesters. The developed method is simple, mild, and general route for the preparation of diversely functionalized 2-aminothiazoles in good to moderate yields from readily available starting materials.     

Quantitative link between single-particle dynamics and static structure of supercooled liquids

We present evidence via molecular simulation that the supercooled fluid states of SPC/E water as well as the "repulsive" and "attractive" supercooled fluid states of a recently introduced model for colloids with short-ranged attractions are characterized by the same functional relationship between self-diffusivity and the pair correlation function. We discuss how this simple relationship connects to an earlier finding that the temperature dependency of a supercooled fluid's single-particle dynamics tracks that of its excess entropy (relative to ideal gas). The generality of this observed structure-property relationship is supported by its ability to successfully describe the nontrivial behaviors of these very different types of model systems.     

Energy and photoinduced electron transfer in a wheel-shaped artificial photosynthetic antenna-reaction center complex

Functional mimics of a photosynthetic antenna-reaction center complex comprising five bis(phenylethynyl)anthracene antenna moieties and a porphyrin-fullerene dyad organized by a central hexaphenylbenzene core have been prepared and studied spectroscopically. The molecules successfully integrate singlet-singlet energy transfer and photoinduced electron transfer. Energy transfer from the five antennas to the porphyrin occurs on the picosecond time scale with a quantum yield of 1.0. Comparisons with model compounds and theory suggest that the F?rster mechanism plays a major role in the extremely rapid energy transfer, which occurs at rates comparable to those seen in some photosynthetic antenna systems. A through-bond, electron exchange mechanism also contributes. The porphyrin first excited singlet state donates an electron to the attached fullerene to yield a P(*+)-C(60)(*-) charge-separated state, which has a lifetime of several nanoseconds. The quantum yield of charge separation based on light absorbed by the antenna chromophores is 80% for the free base molecule and 96% for the zinc analogue.     

Excess-entropy-based anomalies for a waterlike fluid

Many thermodynamic and dynamic properties of water display unusual behavior at low enough temperatures. In a recent study, Yan et al. [Phys. Rev. Lett. 95, 130604 (2005)] identified a spherically symmetric two-scale potential that displays many of the same anomalous properties as water. More specifically, for select parametrizations of the potential, one finds that the regions where isothermal compression anomalously (i) decreases the fluid's structural order, (ii) increases its translational self-diffusivity, and (iii) increases its entropy form nested domes in the temperature-density plane. These property relationships are similar to those found for more realistic models of water. In this work, the authors provide evidence that suggests that the anomalous regions specified above can all be linked through knowledge of the excess entropy. Specifically, the authors show how entropy scaling relationships developed by Rosenfeld [Phys. Rev. A 15, 2545 (1977)] can be used to describe the region of diffusivity anomalies and to predict the state conditions for which anomalous viscosity and thermal conductivity behavior might be found.     

Profiling of Piper betle Linn. cultivars by direct analysis in real time mass spectrometric technique

Piper betle Linn. is a traditional plant associated with the Asian and southeast Asian cultures. Its use is also recorded in folk medicines in these regions. Several of its medicinal properties have recently been proven. Phytochemical analysis showed the presence of mainly terpenes and phenols in betel leaves. These constituents vary in the different cultivars of Piper betle. In this paper we have attempted to profile eight locally available betel cultivars using the recently developed mass spectral ionization technique of direct analysis in real time (DART). Principal component analysis has also been employed to analyze the DART MS data of these betel cultivars. The results show that the cultivars of Piper betle could be differentiated using DART MS data.     

Pulse radiolytic studies of metallic clusters in a quaternary microemulsion system

The radiation-chemical reduction of Tl⁺, Co²⁺ and Ni²⁺ ions in water-in-oil microemulsion has been described. Rate constants for the reduction of the metal ions by e^- _aq were found to be much lower compared to those in aqueous solution. The absorption spectrum and the rate constants of formation of the transient intermediates of metal clusters were correlated with the water-pool size, surrounding environment and compared with data in aqueous solution. Tl₂ ⁺ reacts with Cd²⁺ with k = 1.1 × 10⁸ M^-1 s^-1. Reactions of Tl₂ ⁺ and Co⁺ with Ag⁺ leads to the formation of Ag metal particles. No reaction was observed from Cd⁺ to Tl⁺ or Co²⁺. The results are discussed in terms of dynamic exchange of materials between the polar cores of microemulsion. This exchange facilitates formation of silver particles.     

Control of vortex shedding behind circular cylinder for flows at low Reynolds numbers

It has been observed by researchers in the past that vortex shedding behind circular cylinders can be altered, and in some cases suppressed, over a limited range of Reynolds numbers by proper placement of a second, much smaller, ‘control’ cylinder in the near wake of the main cylinder. Results are presented for numerical computations of some such situations. A stabilized finite element method is employed to solve the incompressible Navier–Stokes equations in the primitive variables formulation. At low Reynolds numbers, for certain relative positions of the main and control cylinder, the vortex shedding from the main cylinder is completely suppressed. Excellent agreement is observed between the present computations and experimental findings of other researchers. In an effort to explain the mechanism of control of vortex shedding, the streamwise variation of the pressure coefficient close to the shear layer of the main cylinder is compared for various cases, with and without the control cylinder. In the cases where the vortex shedding is suppressed, it is observed that the control cylinder provides a local favorable pressure gradient in the wake region, thereby stabilizing the shear layer locally. Copyright © 2001 John Wiley & Sons, Ltd.     

A Fourier–Chebyshev spectral collocation method for simulating flow past spheres and spheroids

An accurate Fourier–Chebyshev spectral collocation method has been developed for simulating flow past prolate spheroids. The incompressible Navier–Stokes equations are transformed to the prolate spheroidal co‐ordinate system and discretized on an orthogonal body fitted mesh. The infinite flow domain is truncated to a finite extent and a Chebyshev discretization is used in the wall‐normal direction. The azimuthal direction is periodic and a conventional Fourier expansion is used in this direction. The other wall‐tangential direction requires special treatment and a restricted Fourier expansion that satisfies the parity conditions across the poles is used. Issues including spatial and temporal discretization, efficient inversion of the pressure Poisson equation, outflow boundary condition and stability restriction at the pole are discussed. The solver has been validated primarily by simulating steady and unsteady flow past a sphere at various Reynolds numbers and comparing key quantities with corresponding data from experiments and other numerical simulations. Copyright © 1999 John Wiley & Sons, Ltd.