Identification of potential anti-obesity drug scaffolds using molecular modelling

Abstract

The prevalence of obesity has remarkably increased in recent decades. An important strategy to combat obesity is to reduce the imbalance between energy intake and expenditure. Pancreatic lipase (PL) and acetyl coenzyme A carboxylase 2 (ACC2) are two promising targets for the therapeutic treatment of obesity. In silico techniques including high throughput virtual screening, binding free energy calculations, and molecular dynamics (MD) simulation were used to identify molecules with good potential to inhibit these targets. Derivatives of coumaran-3-one and dioxabicyclo[3.3.0]octane-2,6-diamine are likely to possess inhibitory potential against PL while acetamide and hexanamide derivatives showed inhibitory potential against ACC2. MD simulations of the top scoring molecules confirmed that the identified molecules bind strongly and consistently in the binding site of PL and ACC2. The shortlisted molecules exhibited better interactions and affinity when compared to control molecules and thus could be explored as scaffolds for the development of anti-obesity drugs.