Computer modelling of monoamine oxidases

The article summarized results of long-term studies on active site structures of monoamine oxidase (MAO) performed in the Institute of Biomedical Chemistry (Russia) by computer modeling approaches. In mammals MAO exists in two highly homologous forms, MAO A and MAO B, distinguished by substrate specificity, inhibitor selectivity, and other characteristics. The development of approaches for active site modeling of these enzymes (with unknown three-dimensional structures) was originally based on analysis of inhibitory activity of selective inhibitors. It started from the analysis of relationships between the geometrical sizes of conformationally rigid molecules and their inhibitory activity. These studies resulted in molding of the active site structures of MAO A and MAO B. These molds reflect the sizes and shapes of active sites of these enzymes. These mold models have been used for virtual screening of molecular databases for new selective and non-selective MAO inhibitors. The generated models have been compared with three-dimensional structures of MAO A and MAO B, which appeared later. © 2015, Pleiades Publishing, Ltd.