Ab initio molecular simulations for proposing novel peptide inhibitors that binds specifically to urokinase receptor.

Abstract

Recent biochemical experiments have revealed that many proteases play important roles in cancer invasion and metastasis. Among these proteases, the binding of urokinase-type plasminogen activator (uPA) and uPA receptor (uPAR) existing on the surface of a cancer cell is a trigger for cancer invasion. Therefore, the blocking of the binding is expected to inhibit cancer invasion. In the present study, we created a various types of peptides for blocking the ligand-binding pocket of uPAR. The binding energies between uPAR and the peptides were evaluated by ab initio//fragment molecular orbital calculations, and the peptide with the largest binding energy was proposed as a potent inhibitor to cancer invasion.