Pairwise decomposition of residue interaction energies using semiempirical quantum mechanical methods in studies of protein-ligand interaction

Pairwise decomposition of the interaction energy between molecules is shown to be a powerful tool that can increase our understanding of macromolecular recognition processes. Herein we calculate the pairwise decomposition of the interaction energy between the protein human carbonic anhydrase II (HCAII) and the fluorine-substituted ligand N-(4-sulfamylbenzoyl)benzylamine (SBB) using semiempirical quantum mechanics based methods. We dissect the interaction between the ligand and the protein by dividing the ligand and the protein into subsystems to understand the structure-activity relationships as a result of fluorine substitution. In particular, the off-diagonal elements of the Fock matrix that is composed of the interaction between the ionic core and the valence electrons and the exchange energy between the subsystems or atoms of interest is examined in detail. Our analysis reveals that the fluorine-substituted benzylamine group of SBB does not directly affect the binding energy. Rather, we find that the strength of the interaction between Thr199 of HCAII and the sulfamylbenzoyl group of SBB affects the binding affinity between the protein and the ligand. These observations underline the importance of the sulfonamide group in binding affinity as shown by previous experiments (Maren, T. H.; Wiley: C. E. J. Med. Chem. 1968, 11, 228-232). Moreover, our calculations qualitatively agree with the structural aspects of these protein-ligand complexes as determined by X-ray crystallography.     

Rapid crack growth in a thermoelastic solid under mixed-mode thermomechanical loading

A two-dimensional steady-sate analysis of semi-infinite brittlecrack growth at a constant subcritical rate in an unboundedfully-coupled thermoelastic solid under mixed-mode thermomechanicalloading is made. The loading consists of normal and shear tractionsand heat fluxes applied as point sources (line loads in theout-of-plane direction). A related problem is solved exactly in an integral transformspace, and robust asymptotic forms used to reduce the originalproblem to a set of integral equations. The equations are partiallycoupled and exhibit operators of both Cauchy and Abel types,yet can be solved analytically. The temperature change field at a distance from the moving crackedge is then constructed, and its dominant term is found tobe controlled by the imposed heat fluxes. The role of this termis, indeed, enhanced if the heat fluxes serve to render thecrack as a net heat source/sink for the solid, as opposed tobeing a transmitter of heat across its plane. More generally,the influence of the thermoelastic coupling on this field, aswell as other functions, is found to increase with crack speed.     

Regulating complex dynamics in firms and economic systems

The decisions of economic firms are often guided by simple routines. We demonstrate that such a routine may generate suboptimal chaotic dynamics, where the suboptimality is due to the fact that decision outcomes are in regions of low performance. We discuss a simple, but effective, method to regulate such dynamics in order to improve the performance. The method works as follows: In a first step, from time series information one has to identify critical starting areas which may lead to a crash or an outcome with low performance. In a second step, one has to perturb the system when it enters these critical areas. Due to sensitive dependence on initial conditions, already minor interventions suffice to prevent harmful events and to obtain better results.     

Evaluation of extraction methods for quantification of aqueous fullerenes in urine

There is a growing concern about the human and environmental health effects of fullerenes (e.g., C(60)) due to their increasing application in research, medicine, and industry. Toxicological and pharmacokinetic research requires standard methods for extraction and detection of fullerenes from biological matrices such as urine. The present study validates the use of liquid-liquid extraction (LLE) and solid-phase extraction (SPE) methods in conjunction with liquid chromatography-mass spectrometry (LC-MS) for the quantitative determination of C(60) in human and synthetic urine as compared with ultrapure water. Glacial acetic acid, which is necessary to prevent emulsions during LLE, inhibited C(60) detection by LC-MS, but this could be mitigated with evaporation. Aqueous C(60) aggregates (nC(60)) were spiked at 180 μg/L into the components of a synthetic urine recipe to determine their individual impacts on extraction and detection. Urea, creatinine, and a complex protein (i.e., gelatin) were found to impair SPE, leading to a low recovery rate of 43 ± 4% for C(60) spiked into human urine. In contrast, C(60) was consistently recovered from synthetic matrices using LLE, and recovery in human urine was 80 ± 6%. These results suggest that LLE combined with LC-MS is suitable for studying the clearance of fullerenes from the body. LLE is a robust technique that holds promise for extracting C(60) from other complex biological matrices (e.g., blood, sweat, amniotic fluid) in toxicological studies, enabling a better understanding of the behavior of fullerenes in human and animal systems and facilitating a more comprehensive risk evaluation of fullerenes.     

Nonlinear asset-price dynamics and stabilization policies

Nonlinear Dynamics - We first present a brief review of nonlinear asset-pricing models and contributions in which such models have been used as benchmarks to evaluate the effectiveness of a number...     

Synthetic magnetic opals

We present studies of novel nanocomposites of BiNi impregnated into the structure of opals as well as inverse opals. Atomic force microscopy and high resolution elemental analyses show a highly ordered structure and uniform distribution of the BiNi filler in the matrix. These BiNi-based nanocomposites are found to exhibit distinct ferromagnetic-like ordering with transition temperature of about 675 K. As far as we know there exists no report in literature on any BiNi compound which is magnetic.     

Speculative Behavior and Asset Price Dynamics

This paper deals with speculative trading. Guided by empirical observations, a nonlinear deterministic asset pricing model is developed in which traders repeatedly choose between technical and fundamental analysis to determine their orders. The interaction between the trading rules produces complex dynamics. The model endogenously replicates the stylized facts of excess volatility, high trading volumes, shifts in the level of asset prices, and volatility clustering.     

Beyond nC60: strategies for identification of transformation products of fullerene oxidation in aquatic and biological samples

Owing to their exceptional properties and versatility, fullerenes are in widespread use for numerous applications. Increased production and use of fullerenes will inevitably result in accelerated environmental release. However, study of the occurrence, fate, and transport of fullerenes in the environment is complicated because a variety of surface modifications can occur as a result of either intentional functionalization or natural processes. To gain a better understanding of the effect and risk of fullerenes on environmental health, it is necessary to acquire reliable data on the parent compounds and their congeners. Whereas currently established quantification methods generally focus on analysis of unmodified fullerenes, we discuss in this review the occurrence and analysis of oxidized fullerene congeners (i.e., their corresponding epoxides and polyhydroxylated derivatives) in the environment and in biological specimens. We present possible strategies for detection and quantification of parent nanomaterials and their various derivatives.