A new, non-polarizable force field model (FFM) for imidazolium-based, room-temperature ionic liquids (RTILs), 1-ethyl-3-methyl-imidazolium tetrafluoroborate and 1-butyl-3-methyl-imidazolium tetrafluoroborate, has been developed. Modifying the FFM originally designed by Liu et al. (J. Phys. Chem. B, 2004, 108, 12978-12989), the electrostatic charges on interacting sites are refined according to partial charges calculated by explicit-ion density functional theory. The refined FFM reproduces experimental heats of vaporization, diffusion coefficients, ionic conductivities, and shear viscosities of RTILs, which is a significant improvement over the original model (Zh. Liu, Sh. Huang and W. Wang, J. Phys. Chem. B, 2004, 108, 12978-12989). The advantages of the proposed procedure include clarity, simplicity, and flexibility. Expanding the functionality of our FFM conveniently only requires modification of the electrostatic charges. Our FFM can be extended to other classes of RTILs as well as condensed matter systems in which the ionic interaction requires an account of polarization effects. © 2011 the Owner Societies.

In the present work, Dempster-Shafer Theory (DST) was employed for the implementation of a combined strategy for classification and/or virtual screening of potential anticoccidial drug candidates, based on the combination of the information provided by multiple QSAR models which are derived from different molecular structure representations. The application of such a strategy lead to a classification performance superior to the individual use of QSAR models, achieving accuracy/sensibility/specificity values over 94%/86%/96% and 86%/75%/89% on training and predicting series, respectively. Parallely, the application of such a strategy lead to values of enrichment metrics significantly superiors to the individual use of QSAR models as virtual screening tools. All these results suggest that the use of DST as the theoretical probabilistic base for the implementation of a combined classification and/or virtual screening strategy can be efficiently employed on the process of discovery and development of novel potential anticoccidial candidates, contributing in this way to overcome the emergence of resistance to current therapies.

Potent and selective ligands with a nucleoside skeleton are generally thought as agonists of the human A(3) adenosine receptor (AR), however, some of them can also act as full antagonists. This work reports a Quantitative Structure-Activity Relationship (QSAR) study for predicting the binding affinity of such type of compounds towards the A(3) AR. Several different theoretical molecular descriptors, calculated only on the basis of knowledge of the molecular structure and an efficient variable selection procedure, such as forward stepwise regression, led to models with satisfactory accuracy and predictive ability. But the best-final QSAR model is based on the Molecule Representation of Structures based on Electron diffraction (3D-MoRSE) descriptors capturing a reasonable interpretation. This QSAR model is able to explain more than 85% of the variance in the experimental affinity and manifests good predictive ability as indicated by the higher Q(2)s of cross-and external-validations. The model obtained in this study may provide guidance for future design of new potent and selective human A(3) AR full antagonists with a nucleoside skeleton.

Background: The mechanism(s) responsible for breast capsular contracture (CC) remain unknown, but inflammatory pathways play a role. Various molecules have been attached to implant shells in the hope of modifying or preventing CC. The intrinsic antibacterial and antifungal activities of chitosan and related oligochitosan molecules lend themselves well to the study of the infectious hypothesis; chitosan's ability to bind to growth factors, its hemostatic action, and its ability to activate macrophages, cause cytokine stimulation, and increase the production of transforming growth factor (TGF)-beta 1 allow study of the hypertrophic scar hypothesis. Objective: The authors perform a comprehensive evaluation, in a rabbit model, of the relationship between CC and histological, microbiological, and immunological characteristics in the presence of a chitooligosaccharide (COS) mixture and a low molecular weight chitosan (LMWC). Methods: Eleven adult New Zealand rabbits were each implanted with three silicone implants: a control implant, one impregnated with COS, and one impregnated with LMWC. At four-week sacrifice, microdialysates were obtained in the capsule-implant interfaces for tumor necrosis factor alpha (TNF-alpha) and interleukin-8 (IL-8) level assessment. Histological and microbiological analyses were performed. Results: Baker grade III/IV contractures were observed in the LMWC group, with thick capsules, dense connective tissue, and decreased IL-8 levels (p < .05) compared to control and COS groups. Capsule tissue bacterial types and microdialysate TNF-alpha levels were similar among all groups. Conclusions: Chitosan-associated silicone implantation in a rabbit model resulted in Baker grade III/IV CC. This preclinical study may provide a model to test various mechanistic hypotheses of breast capsule formation and subsequent CC.

Human herpes viruses (HHV) are leading cause of human viral diseases, second after influenza and cold viruses. They cause overt disease or can remain silent for many years waiting for reactivation. HHV are associated to several side-effects or co-conditions like Alzheimer's disease, cholangiocarcinoma and pancreatic cancer, and with the time, they have become resistant to the available commercial drugs like acyclovir, whose final target is the DNA-polymerase. For this reason there is an increasing interest for the search of novel compounds against herpes viruses. In this sense, Bioinformatics is determinant for a better understanding of the mechanisms of resistance, and also for the search of new biomolecular targets for the design of more potent and versatile anti-herpes agents. This review is focused on the role of Bioinformatics toward the design of compounds with anti-herpetic activity and also we propose a model based fragment descriptors for the design, search and prediction of anti-herpes compounds through the inhibition of 5 targets belonging to different herpes viruses.

The adsorption energies and the activation energy barriers for a series of reactions catalyzed by gold surfaces and obtained theoretically through density functional theory (DFT) based calculations were considered to clarify the role of the low coordinated gold atoms and the role of doping in the catalytic activity of gold. The effect of the surface steps was introduced by comparison of the activation energy barriers and of the adsorption energies on flat gold surfaces such as the Au(111) surface with those on stepped surfaces such as the Au(321) or the Au(110) surfaces. It is concluded that the presence of low coordinated atoms on the latter surfaces increases the adsorption energies of the reactants and decreases the activation energy barriers. Furthermore, the increasing of the adsorption energy of the reaction products can lead to lower overall reaction rates in the presence of low gold coordinated atoms due to desorption limitations. On the other hand, the effect of doping gold surfaces with other transition metal atoms was analyzed using the dissociation reaction of molecular oxygen as a test case. The calculations showed that increasing the silver content in some gold surfaces was related to a considerable increment of the reactivity of bimetallic systems toward the oxygen dissociation. Importantly, that increment in the reactivity was enhanced by the presence of low coordinated atoms in the catalytic surface models considered.

The plasma concentration of HDL-C and the prevalence of coronary heart disease (CHD) is inversely related. Inhibition of cholesteryl ester transfer protein (CETP) is considered to be a potential approach to treat dyslipidemia and CHD. 2-arylbenzoxazoles were found to be a potential class of CETP inhibitors. A 2D QSAR study was done on a series of 2-arylbenzoxazoles using PCR, PLS and MLR techniques and externally validated to determine significant models. kNN-MFA 3D QSAR was performed on the same series to correlate the effects of electrostatic, steric and hydrophobic parameters with the CETP inhibitory activity using forward backward regression, genetic algorithm and simulated annealing methods. Pharmacophore mapping was also done on the conformers of the 2-arylbenzoxazoles generated by the BEST and the FAST method. This work may provide a platform for generating leads for novel CETP inhibitors. © 2011 The Royal Society of Chemistry.