Molecular docking of curcumin analogues as serca inhibitory agents

Abstract

Сurcumin derivatives were virtually screened for inhibitory activity towards SERCA by computational docking. A detailed characterization of the inhibitor binding site at the molecular level and determination of the amino acids involved in interactions with curcumin and its derivatives have been provided. Crucial enzyme/inhibitor interactions were identified by analyzing the docking-predicted binding poses of active compounds. The loss of hydrophilic group by curcumin leads to an increase in binding energy. Some of curcumin derivatives showed better docking energies than curcumin indicating that they could be potent enzyme inhibitors. Additional binding energy was provided by extensive hydrophobic interaction between the hydrophobic parts of the ligands and the nonpolar residues at the binding site. Curcumin derivatives satisfy Lipinski’s Rule of five which testifies to their druglikeness (absorption, distribution, metabolism and excretion) and possible pharmacological activity.

Keywords

• molecular docking
• binding energy
• binding site
• inhibitors
• apoptosis