A discriminating pharmacophore model for noncompetitive metabotropic glutamate receptor antagonists of subtype 1 (mGluR1) was developed that facilitated the discovery of moderately active mGluR1 antagonists. One scaffold was selected for the design of several focused libraries where different substitution patterns were introduced. This approach facilitated the discovery of potent mGluR1 antagonists, as well as positive and negative mGluR5 modulators, because both receptor subtypes share similar binding pockets. For mGluR1 antagonists, a homology model of the mGlu1 receptor was established, and a putative binding mode within the receptor's transmembrane domain was visualized.

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We consider the problem of light scattering in a slab of cholesteric liquid crystal with the pitch which significantly exceeds the wavelength of light. The electromagnetic wave propagation and the Green's function are investigated for this medium basing on geometric optics approximation. The correlation function of the director fluctuations is calculated with the aid of the vector analog of the WKB approximation. A general approach to treatment of single light scattering in a stratified medium with smoothly varying properties based on the Kirchhoff method is developed. Angular and polarization dependencies of the single light scattering intensity as well as extinction of the mean field are analyzed. Unusual dependence of the light scattering intensity on the size of the system is found.

The Fréedericksz transition in twist cells of cholesteric liquid crystals with a finite surface energy is considered. It is shown that this transition can be either of the second order or of the first order depending on the values of the Frank constants, pitch, surface energies, and the cell thickness. A simple criterion that determines the order of the phase transition is obtained. By numerically minimizing the free energy of the liquid-crystal pattern the distribution of the director in the presence of the external electric field is calculated. For this purpose the polar angle of the director was presented as a partial sum of the Fourier series and of the appropriate function. The azimuthal angle was eliminated using Euler-Lagrange equations. Calculations were performed for different sets of liquid-crystal parameters which provide the phase transition of the first and of the second order. The numerical results are in a good agreement with theoretical formulas based on the Landau-type theory.

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