Analysis of the Interactions between Arp2/3 Complex and an Inhibitor Arpin by Molecular Dynamics Simulation

The Arp2/3 complex is one of the main regulators of the actin cytoskeleton and a basic molecular machine that nucleates the branched actin filaments. In this work, we studied the interaction of the Arp2/3 complex with its inhibitor, arpin, and revealed the amino-acid residues that are responsible for complex formation. The free-energy calculation for arpin binding to the Arp2/3 complex was performed using umbrella sampling. It has been shown that the dissociation constant of the Arp2/3–arpin complex is higher on average than that of Arp2/3 complexes with other inhibitors. Two arpin binding sites with different affinities were identified on the surface of the Arp2/3 complex. The mechanism of the inhibition of the Arp2/3 complex by arpin is discussed.