Finding small molecule ligand for affinity purification of human coagulation factor VIII by means of the in silico molecular docking

In silico docking was used to select a group of new candidate synthetic affinity ligands for purification of recombinant blood coagulation factor VIII. Previously designed by Kessler and coworkers peptide ligands L3 and L4, reversibly binding factor VIII molecule, were used as reference compounds. Assumed binding sites of these compounds were located at C1 or/and С2 domains of the protein.
In the present work we have modelled the interaction of L3 and L4 compounds with theoretically proposed binding surfaces, located at apex regions of C1 and C2 domains. It was found that both compounds bind to the mapped surfaces with significant composite docking indexes. These surfaces were used for in silico docking of intact and modified virtual compound libraries from Asinex and Chembridge suppliers. The final docking scores of the top candidates from both libraries are of the same range and closely correspond to docking scores of reference compounds. Trimming of the initial library and modification of compounds molecules by the linker group, performed by simple Perl scripts before the docking run dramatically increased both calculation efficiency and chemical relevance of top candidates. Small subset of ligand candidates will be further tested for affinity and reversibility of factor VIII binding.