Discovery of novel small molecular ligands for TLR۸ by computational methods

The TOLL-like receptor ۸ (TLR۸) is an endosomal protein expressed in some of the innate immune cells andinvolved in viral infections. however, many recent studies are available, to prove their role in forminganticancer responses. This study aimed at the virtual screening of a great number of compounds to detectligands with appropriate pharmacological properties. with this purpose, PDB codes of TLR۸ in complex withits agonists were studied and a pharmacophore model was designed for each of them by using the Pharmitwebserver. In the next step, all compounds available in two great databases, ZINC and Pubchem werescreened by these models. Afterward, several filters were applied to detect the ADME-Tox features by useof the FAF-Drugs۴ server. Then all the output compounds were docked to the TLR۸ receptor. Subsequently,the highest docking scores were prepared for Molecular Dynamics (MD) simulation with GROMOS۴۳a۱energy field by GROMACS software in ۲۰ns. The result demonstrated two compounds are great candidatesfor further pharmaceutical studies for discovering either antiviral or anticancer medicines in the future.

Keywords:

Toll-like receptor ۸ , Virtual screening , Docking , Molecular Dynamics Simulation