Role of invariant water molecules in retaining the active site geometry of β-lactamase: a molecular dynamics simulation study

Abstract

Water molecules play a critical role in stabilising the three-dimensional architecture, dynamics and function of biological macromolecules. Comparative analysis of structurally similar proteins has shown that there are water molecules conserved in the same relative positions and make similar hydrogen bonds with proteins in all crystal structures. These invariant water molecules are essential for the maintenance of the native structure of proteins. The present study explores the role of invariant water molecules to maintain the active site geometry of β-lactamase enzyme. Thirteen crystal structures of class-A β-lactamase from Staphylococcus aureus have been used in this study. Molecular dynamics simulations of the protein structures were performed in hydrated as well as in dehydrated conditions. The analysis showed that significant changes occur in the active site geometry due to dehydration. These changes can be attributed to the removal of water molecules at the active site.