Equilibrium Molecular Dynamics of the Monomer and Dimer Units of Streptococcus Pnuemonae and Corynebacterium Diphtheriae Pili

Abstract

Pili are elongated protein structures that enhance the adhesive abilities and virulence of bacteria. As a result, it is important to understand their structure and mechanical properties. Pili are constructed by joining monomeric units (or pilins) into polymeric fibers via intermolecular isopeptide bonds. Interestingly, the pilins additionally possess intramolecular isopeptide bonds that are formed between the sidechains of lysine and asparagine residues in the same domain of the protein, which are believed to impart mechanical stability to the pili. In this work, we use all atom molecular dynamics simulations to study the conformational dynamics of monomeric and dimeric forms of the pilins of streptococcus pnuemonae (RrgB) and corynebacterium diphtheriae (spaA) in the presence and absence of intramolecular isopeptide bonds. The results reveal how the energetics and dynamics of these subunits are affected by intramolecular isopeptide bonds, and demonstrate how they affect pili stability.