Structure based interaction and molecular dynamics studies of cysteine protease Cathepsin B against curcumin and resveratrol

Abstract

The lysosomal cysteine peptidase Cathepsin B is identified as a pivotal contributor to cancer development. In the pursuit of discovering less toxic inhibitors for Cathepsin B, various organic compounds have undergone thorough investigation and are being studied at the moment in clinical studies for cancer treatment. Notably, curcumin and resveratrol emerge as prominent candidates. However, the precise molecular mechanism underlying the inhibition of Cathepsin B by these compounds remains elusive. To address this gap, we conducted molecular docking and dynamics studies to unravel the interaction dynamics between Cathepsin B and phytochemicals such as curcumin and resveratrol. Remarkably, Molecular docking studies revealed that curcumin and resveratrol exhibit high binding affinities 7.599 and 6.103 kcal/mol, respectively, positioning them as promising inhibitors for Cathepsin B. Further insights from 150 ns of molecular dynamics simulations, incorporating structural analyses encompassing RMSF, RMSD, Rg, SASA, and H-bond analysis, indicate the superior stability of curcumin compared to resveratrol. Additionally, we assessed their drug-likeness properties using the PreADMET web server, and the MM/BPSA method facilitated the calculation of binding energies for the complexes. On targeting Cathepsin B, this research promises to contribute to the development of drugs that inhibit the progression of cancer.

Keywords: Cathepsin B; MD-simulation; MM/PBSA; SASA; curcumin; preADMET; resveratrol.