Investigation of Dipeptidyl Peptidase 3 as a Heart Failure Inhibitor Target Using Molecular Docking, Molecular Dynamics, and ADMET Predictions

Abstract

Heart failure (HF) remains a leading cause of global mortality, driving the search for novel therapeutic targets. Dipeptidyl Peptidase 3 (DPP3), a zinc dependent aminopeptidase, disrupts cardiovascular homeostasis by degrading angiotensin peptides and has emerged as a promising candidate. This study employed an integrated computational approach to investigate DPP3 inhibition. High-throughput virtual screening and molecular docking identified two compounds, Cmpd 1 and Cmpd 2, with high predicted binding affinity (-9.5 kcal/mol and -8.7 kcal/mol, respectively). Subsequent 100 ns molecular dynamics simulations demonstrated stable complex formation, with protein backbone RMSD values below 2.1 Å. Pharmacokinetic and toxicity profiling indicated favorable drug-like properties for both compounds. Our findings suggest these ligands are promising starting points for developing DPP3 inhibitors for heart failure treatment.