Degradation of Novichok nerve agent A234 by phosphotriesterase: insight into the pH-regulated mechanism from QM/MM and MM MD simulations

Key Points

• The aim is to understand how pH affects the hydrolysis of the Novichok nerve agent A234 by phosphotriesterase.
• Conducted quantum mechanics/molecular mechanics (QM/MM) simulations
• Performed molecular dynamics (MD) simulations at varying pH levels
• Analyzed the hydrolytic mechanism of the S p-enantiomer A234
• Identified a pH-dependent mechanism for the degradation of A234
• Demonstrated increased activity of phosphotriesterase at specific pH levels
• Provided insights into molecular interactions during the hydrolysis process