Characterising ATP binding activity of PilB ATPase of Shewanella oneidensis MR-1 using a molecular modeling and simulations approach

Abstract

This study characterises the interaction between the type IV pilus assembly PilB ATPase of a versatile electroactive microbe, Shewanella oneidensis MR-1, and ATP using in silico tools. PilB ATPase, which is associated with different cellular activities, is a protein subunit of type IV pili. A composite model of the protein was generated using the I-TASSER Web server and its stereochemical quality was evaluated using PROCHECK. Loop modeling was performed using the InteractiveRosetta tool to refine the structure of the model and the COACH server was used to identify the functional binding site. The nature of binding, with the native ligand ATP, was determined using Autodock Vina and Discovery Studio Visualizer. Molecular dynamics simulations were carried out, with the bound and unbound states of the protein, for a period of 100 ns using GROMACS. Favorable root mean square deviation (0.75±0.10 nm) and radius of gyration (2.78±0.05 nm) values pointed to the stability of the modeled protein structure. Root mean square fluctuation and solvent accessible surface area analyses indicated a conformational change upon the ligand binding which occurred without a corresponding reorganization of secondary structures as evidenced by definition of secondary protein analysis. Molecular mechanics/Poisson-Boltzmann surface area analysis revealed the presence of a loop critical to the formation of stable interactions with ATP.