VALIDATION THROUGH RE-DOCKING, CROSS-DOCKING AND LIGAND ENRICHMENT IN VARIOUS WELL-RESOLUTED MAO-B RECEPTORS

Molecular docking is one of the most utilized in silico techniques, which drastically reduces the cost and the time needed for the design of novel drugs. Recently, the tremendous growth of resolved crystallographic MAO-B structures, together with the rapidly rising computing power, has resulted in accelerated and moderately correct docking studies. However, initial validations of the docking protocols prior to virtual screening are required, considering the diverse set of scoring functions and the high number of crystallographic structures with different conformations. In this study, we conducted self- and cross-docking simulations of 21 highly resolute MAO-B receptors utilizing the docking software GOLD 5.3. The crystallographic structures with codes 1S3B, 3PO7, and 6FVZdemonstrated the most prominent ability to accommodate a chemically diverse set of ligands with good RMSD values. In some cases, higher enrichments were observed when rigid docking was carried out. The PDB code 1S3B demonstrated the highest modified enrichment value of 8.33. The latter structure could be further examined through ensemble and side-chain flexible dockings in order to obtain enhanced enrichments for a future virtual high-throughput screening.