Abstract
Maternal embryonic leucine zipper kinase (MELK) is of vital importance due to its significant role in cancer development and its association with poor prognosis in different cancers. Here, we employed several computer aided drug design approaches to shortlist potential binding molecules of MELK. For virtual screening, asinex oncology library (containing 6334 drugs) and comprehensive marine natural products database (containing approximately 32,000 drugs) were used. The study identified two drug molecules: Top-2 and Top-3 as high affinity binding MELK molecules compared to the control co-crystalized Top-1 inhibitor. Both the shortlisted compounds and the control showed high stable binding free energy and high GOLD score. The compounds and control also reported stable dynamics with root mean square deviations (RMSD) value ti 2 A in 500 ns. Similarly, the MELK active site residues were observed in good stability with the compounds. Further, it was noticed the compounds/control formed multiple hydrogen bonds with the MELK active pocket residues which is the main reason of high intermolecular stability. Atomic level binding free energies determined van der Waals and electrostatic energies to play vital role in stable complex formation. From drug likeness and pharmacokinetics perspective, the compounds are ideal molecules for further investigation. Overall, the results are promising and might be tested in in vivo and in vitro studies against MELK. (c) 2022 The Author. Published by Elsevier B.V. on behalf of King Saud University.