Ionic strength effects on the association funnel of barnase and barstar investigated by Brownian dynamics simulations

In this paper, we have studied the effects of ionic strength on the diffusional association behavior of barstar and barnase according to Brownian dynamics simulations. Through detailed analysis of the simulated trajectories, we have characterized the free-energy profiles along the reaction pathway, the regions of the encounter complex, and the optimal association pathways. It is shown that the association behavior is quite similar at low and moderate ionic strengths, whereas the depth of the association funnel strongly increases with decreasing ionic strengths. In this regime, the encounter complex is located above the interaction patch of barnase, and a second energetically favorable region is located near the RNA-binding loop. During the simulations at low and medium ionic strengths, both regions are highly occupied. At high ionic strengths, the region above the interaction patch of barnase becomes increasingly unfavorable due to shielding of the electrostatic field. This results in a rapid shift of the encounter complex into the region near the RNA-binding loop. Surprisingly, this region is not highly occupied at high ionic strengths. The reason for this is the shallow depth of the free-energy profile. Furthermore, the association appears to be rather isotropic due to the decreased electrostatic steering.