In-silico study of seaweed secondary metabolites as AXL kinase inhibitors

Lavanya Nagamalla; J V Shanmukha Kumar; Chintakindi Sanjay; Ali M Alsamhan; Mohammed Rafi Shaik

doi:10.1016/j.sjbs.2021.11.054

In-silico study of seaweed secondary metabolites as AXL kinase inhibitors

Saudi J Biol Sci. 2022 Feb;29(2):689-701. doi: 10.1016/j.sjbs.2021.11.054. Epub 2021 Nov 30.

Authors

Lavanya Nagamalla¹, J V Shanmukha Kumar¹, Chintakindi Sanjay², Ali M Alsamhan², Mohammed Rafi Shaik³

Affiliations

¹ Department of Chemistry, Koneru Lakshmaiah Education Foundation, Vaddeswaram, A.P., India.
² Industrial Engineering Department, College of Engineering, King Saud University, P.O. Box. 800, Riyadh 11451, Saudi Arabia.
³ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.

Abstract

AXL kinase is an attractive cancer target for drug design and it is involved in different cancers. A set of molecule databases with 1072 secondary metabolites from seaweeds were screened against the AXL kinase active site and eight molecules were shortlisted for further studies. From the docking analysis of the complexes, four molecules GA011, BE005, BC010, and BC005 are showing prominent binging. From the 100 ns of molecular dynamics simulations and ligand-bound complex MM-PBSA free energy analysis, two molecules BC010 (ΔG = -135.38 kJ/mol) and BE005 (ΔG = -141.72 kJ/mol) are showing molecule stability in the active site also showing very strong binding free energies. It suggests these molecules could be the potent molecules for AXL kinase.

Keywords: AXL kinase; Cancer therapy; Marine species; Molecular dynamics simulations; Secondary metabolites; Virtual screening.