Identification of hits as anti-obesity agents against human pancreatic lipase via docking, drug-likeness, in-silico ADME(T), pharmacophore, DFT, molecular dynamics, and MM/PB(GB)SA analysis

Abstract

Obesity, characterized by excessive fat accumulation, is a major health concern. Inhibition of human pancreatic lipase, an enzyme involved in fat digestion, offers a potential strategy for weight loss and obesity treatment. This study aimed to identify polyphenols capable of forming stable complexes with human pancreatic lipase to block its activity. Molecular docking, density functional theory (DFT), molecular dynamics (MD) simulations, and MMPBGBSA calculations were employed to evaluate ligand binding, stability, and energy profiles. Pharmacophore modeling was also performed to identify key structural features for effective inhibition. Virtual screening identified ZINC000015120539, ZINC000000899200, ZINC000001531702, and ZINC000013340267 as potential candidates, exhibiting favorable binding and stable interactions over 100 ns MD simulations. These findings provide insights into the inhibitory potential of selected polyphenols on human pancreatic lipase and support further experimental investigations for obesity treatment.

Communicated by Ramaswamy H. Sarma

Keywords:

• Molecular docking
• molecular dynamics
• obesity
• pancreatic lipase
• polyphenol

Disclosure statement

The authors declare no conflicts of interest concerning to the authorship, research work, and/or publication of this work.

Additional information

Funding

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