Supercomputer Search for the New Inhibitors of the Coagulation Factor XIIa

A virtual structure-oriented screening of candidates for inhibitors of blood coagulation factor XIIa was carried out. This coagulation factor is one of the most promising therapeutic targets for the development of anticoagulants without disturbing normal hemostasis. The screening was carried out in the database of organic compounds of the Voronezh State University, consisting of more than 19 thousand molecules. At the first stage of virtual screening, ligands were positioned in the active center of factor XIIa using the SOL docking program. At the second stage, for the best ligands, the protein-ligand binding enthalpy was calculated using the MOPAC program and the PM7 quantum-chemical method, taking into account the solvent in the COSMO continuum model. All calculations were carried out using the supercomputing resources at Lomonosov Moscow State University. In total, more than 30 thousand ligand conformers are docked, and for more than 400 of the best of them, the protein-ligand binding enthalpy was calculated. 16 compounds are selected as the most promising candidates for subsequent in vitro testing of their ability to inhibit factor XIIa.