Pyrone-based inhibitors of metalloproteinase types 2 and 3 may work as conformation-selective inhibitors.

Matrix metalloproteinases are zinc-containing enzymes capable of degrading all components of the extracellular matrix. Owing to their role in human disease, matrix metalloproteinase have been the subject of extensive study. A bioinorganic approach was recently used to identify novel inhibitors based on a maltol zinc-binding group, but accompanying molecular-docking studies failed to explain why one of these inhibitors, AM-6, had approximately 2500-fold selectivity for MMP-3 over MMP-2. A number of studies have suggested that the matrix-metalloproteinase active site is highly flexible, leading some to speculate that differences in active-site flexibility may explain inhibitor selectivity. To extend the bioinorganic approach in a way that accounts for MMP-2 and MMP-3 dynamics, we here investigate the predicted binding modes and energies of AM-6 docked into multiple structures extracted from matrix-metalloproteinase molecular dynamics simulations. Our findings suggest that accounting for protein dynamics is essential for the accurate prediction of binding affinity and selectivity. Additionally, AM-6 and other similar inhibitors likely select for and stabilize only a subpopulation of all matrix-metalloproteinase conformations sampled by the apo protein. Consequently, when attempting to predict ligand affinity and selectivity using an ensemble of protein structures, it may be wise to disregard protein conformations that cannot accommodate the ligand

Broad Histogram Method for Continuous Systems: the XY-Model

We propose a way of implementing the Broad Histogram Monte Carlo method to systems with continuous degrees of freedom, and we apply these ideas to investigate the three-dimensional XY-model with periodic boundary conditions. We have found an excellent agreement between our method and traditional Metropolis results for the energy, the magnetization, the specific heat and the magnetic susceptibility on a very large temperature range. For the calculation of these quantities in the temperature range 0.7<T<4.7 our method took less CPU time than the Metropolis simulations for 16 temperature points in that temperature range. Furthermore, it calculates the whole temperature range 1.2<T<4.7 using only 2.2 times more computer effort than the Histogram Monte Carlo method for the range 2.1<T<2.2. Our way of treatment is general, it can also be applied to other systems with continuous degrees of freedom.Comment: 23 pages, 10 Postscript figures, to be published in Int. J. Mod. Phys.

Hamming distance and mobility behavior in generalized rock-paper-scissors models

This work reports on two related investigations of stochastic simulations which are widely used to study biodiversity and other related issues. We first deal with the behavior of the Hamming distance under the increase of the number of species and the size of the lattice, and then investigate how the mobility of the species contributes to jeopardize biodiversity. The investigations are based on the standard rules of reproduction, mobility and predation or competition, which are described by specific rules, guided by generalization of the rock-paper-scissors game, valid in the case of three species. The results on the Hamming distance indicate that it engenders universal behavior, independently of the number of species and the size of the square lattice. The results on the mobility confirm the prediction that it may destroy diversity, if it is increased to higher and higher values.Comment: 7 pages, 9 figures. To appear in EP

Self-Similar Collapse of Scalar Field in Higher Dimensions

This paper constructs continuously self-similar solution of a spherically symmetric gravitational collapse of a scalar field in n dimensions. The qualitative behavior of these solutions is explained, and closed-form answers are provided where possible. Equivalence of scalar field couplings is used to show a way to generalize minimally coupled scalar field solutions to the model with general coupling.Comment: RevTex 3.1, 15 pages, 3 figures; references adde

Line-strength indices and velocity dispersions for 148 early-type galaxies in different environments

We have derived high quality line-strength indices and velocity dispersions for a sample of 148 early-type galaxies in different environments. The wavelength region covered by the observations ($\lambda \simeq 4600$ to 6600 Å) includes the Lick/IDS indices H${\beta}$, Mg1, Mg2, Mgb, Fe5015, Fe5270, Fe5335, Fe5406, Fe5709, Fe5782, NaD, TiO1 and TiO2. The data are intended to address possible differences of the stellar populations of early-type galaxies in low- and high-density environments. This paper describes the sample properties, explains the data reduction and presents the complete list of all the measurements. Most galaxies of the sample (85%) had no previous measurements of any Lick/IDS indices and for 30% of the galaxies we present first-time determinations of their velocity dispersions. Special care is taken to identify galaxies with emission lines. We found that 62 per cent of the galaxies in the sample have emission lines, as measured by the equivalent width of the [OIII] 5007Å line, EW[OIII] > 0.3 Å