Zn2+ ion of the snake venom metalloproteinase (SVMP) plays a critical role in ligand binding: a molecular dynamics simulation study

Abstract

Snake venom metalloproteinase (SVMP) is one of the major components of snake venom and it is a root causative agent for edema, local tissue damage, inflammation, blood coagulation and hemorrhage during the snake bite. The catalytic activity of SVMP is regulated by metal ions (Zn²⁺ and Ca²⁺). In this study, the three dimensional structure of SVMP was modeled with Zn²⁺ and Ca²⁺ ions. Molecular docking, prime/MM-GBSA (ΔG_Bind calculations), quantum polarized ligand docking (QPLD), QM–MM interaction energy analysis and molecular dynamics simulation were performed for the compound Clerodane diterpenoid with the SVMP in the presence and absence of metal ions (Zn²⁺ and Ca²⁺). The result shows that the metal ions are present in the ligand binding domain are critical for the SVMP protein to function, particularly the Zn²⁺ ion. Further, we observed that both the ions have a significant effect on ligand binding.