Characterization of interactions between PilA from Pseudomonas aeruginosa strain K and a model membrane

Type IV pili are important adhesion and motility factors in both gram-negative and gram-positive bacterial species, making pilus assembly from pilin subunits an important biophysical mechanism to understand at an atomic level. Knowledge of the pilus assembly mechanism has applications in antibiotic development, microbial physiology, and systems biology. We applied molecular dynamics simulations to investigate the position and orientation of Pseudomonas aeruginosa strain K PilA in a model membrane as well as the interactions of PilA with the surrounding lipids, identifying several key residues that stabilize the position of PilA within the membrane. Furthermore, we performed umbrella sampling to determine the free energy of extracting this protein from the membrane. Our results provide insight into the molecular events and energetics associated with pilus assembly, thereby initiating a detailed examination of the dynamics of this process.