Dynamics of Uninhibited and Covalently Inhibited Cysteine Protease on Non-physiological pH

Abstract

Differences in activity and the structural stability under simulated gastric juice conditions of uninhibited and covalently inhibited cysteine protease, isolated from the fruit, were experimentally observed. We employed molecular dynamics simulations of proteins modeled from the similar ones with known 3D structure to explain experimental findings. Simulations were performed with NAMD, using CHARMM force field in explicit solvent model. Conformational changes observed in MD trajectories offer indication on differences in stability of inhibited vs. uninhibited protein on low pH values. Protonation states of the protein side chains, through the non-bonded interactions that stabilize 3D structures, likely, significantly contribute to difference in stability of uninhibited and covalently inhibited protein on low pH values.