COMPARISON OF BENZODIAZEPINE-LIKE COMPOUNDS USING TOPOLOGICAL ANALYSIS AND GENETIC ALGORITHMS

Four compounds within a set of ligands for the benzodiazepine receptor s are characterized by their electron density maps at different resolu tion levels and reconstructed from calculated structure factors. The r esulting complex three-dimensional density maps are first simplified i nto connected graphs using topological analysis. Then, an original gen etic algorithm method, GAGS (Genetic Algorithm for Graph Similarity se arch), is developed and implemented in order to compare the connected graphs. Finally, the analysis of the best solutions of the algorithm a re expressed in terms of functional group superimpositions. The GAGS a nalysis is applied to different resolution levels of the electron dens ity maps and the resulting models are compared in order to assess the influence of the resolution on the resulting pharmacophore models.