The initial structure of the protein was taken from the Dihydroergocristine mesylate crystal structure of its complex with TBBt, while the topology and point charges for the ligands were adopted from ab initio calculations. For each ligand, a total of 999 rounds of restricted random docking was performed, and the ensemble of estimated ligand locations was then clustered according to an assumed 3 A �� threshold, found sufficient to distinguish between the two possible proton locations in the symmetrical ligand. The lowest energy-cluster was taken as the structural representation of the complex. Molecular Dynamics analysis was carried out with the aid of the Yasara-Model, using the standard Yasara2 force field, further extended for all ligands by adding ab initio derived topologies and charge distributions. Starting structures of complexes with various ligands were adopted from the crystal structure of CK2a complex with TBBt. All water molecules closer than 6 A �� from the protein in the original PDB structure were preserved, and then a cube with dimensions 78666659 A �� was filled with additional water molecules to give an average solvent density. Coordinates of protein residues distal by more than 6 A �� from the initial ligand location were fixed. Similarly all distal water molecules were fixed. For each of the 16 possible permutations of Br R H replacements, 5 ns MD simulations were performed, and the last 3 ns subjected to more detailed analysis. All the numerical models, including iterative QSAR reduction by means of the lowest eigenvalue vector, were performed using the Marquand algorithm implemented in the GnuPlot program. Long-term alcohol use and dependence alter brain function and are linked to persistent changes in gene expression. Gene expression profiling in human alcoholics and rodent models of binge drinking and dependence have provided insight into the changes in the brain transcriptional landscape resulting from different drinking paradigms; however, to date it is not clear whether transcriptome changes found in animal models of excessive alcohol CHIR 99021 trihydrochloride consumption are consistent with changes found in human alcoholics. Consilience in gene expression would be a key step toward validating animal models by determining commonalities in molecular plasticity between human and rodent brain. Genomic approaches have successfully identified alcohol-mediated changes in gene expression in animal models of alcoholism. These studies suggest that distinct patterns of gene expression underlie specific alcohol-related phenotypes. Animal models of excessive consumption have been developed to investigate different stages of the alcohol abuse cycle that ultimately lead to dependence, including continuous two-bottle choice, drinking in the dark, and chronic intermittent ethanol exposure. In general, studies have focused on transcriptional changes at a single time point following alcohol treatment; thus, it is difficult to determine if the changes in expression patterns are transient or longer lasting. CIE vapor exposure can be used to achieve and maintain high blood ethanol concentrations in C57BL/6J mice, and it results in increased self-administration of ethanol.