Anti-lung cancer drug discovery approaches by polysaccharides: an in silico study, quantum calculation and molecular dynamics study

Abstract

Lung cancer (LC) is one of the major and risky health defects even the serious cause for death in concurrent era. But no potential drugs even chemotherapeutic agents have been discovered with approval of health safety although some non-toxic biological macromolecules, such as polysaccharides and polysaccharide–protein complexes, have obtained as anti-lung cancer properties. This study conveys the anti-lung cancer properties of 45 polysaccharide derivatives collected from PubChem database. Primarily, the PASS prediction was performed to depict their anti-cancer activity, and 37 compounds showed the desired results. Next, the chemical descriptors, such as HOMO, LUMO, softness, and hardness etc, were calculated through the density functional theory (DFT) for quantum properties. Secondly, the auto molecular docking was executed to delineate the protein-ligand interactions, binding ability and inhibition of active sites of proteins. Additionally, the compounds showed docking score more than −6.40 kcal/mol, and the highest binding affinity was at −10.00 kcal/mol even 15 compounds have higher binding score (-8.6 to −10.0) than approved drugs, Gemcitabine. Succeeding, the most common protein residue, VAL 647, was blocked by ligands for the main protein (1X2J). In addition, five protein’s active sites were determined to make the relative study of protein-ligand interactions. As a result, the target docking against five proteins was performed, and it was found that the targeted docking score as the binding affinity is lower than auto docking. Finally, a comparative study between auto docking and targeted docking was performed for the most common five lung cancer proteins founded in three organisms.

Communicated by Ramaswamy H. Sarma

Keywords:

• Pass prediction
• DFT
• Docking
• ADMET
• molecular dynamics

Disclosure statement

No potential conflict of interest was reported by the author(s).

Funding

The author(s) reported there is no funding associated with the work featured in this article.