Anisotropic Diffusion Effects on the Barnase–Barstar Encounter Kinetics

We investigated effects of hydrodynamic anisotropy on the kinetics of a diffusional encounter of a bacterial ribonuclease, barnase, and its natural inhibitor barstar, using the rigid-body Brownian dynamics technique. We performed atomistically detailed Brownian dynamics simulations of barnase and barstar under periodic boundary conditions, taking into account excluded volume and electrostatic and hydrophobic interactions between the proteins. We studied their specific (i.e., orientationally restricted by their configuration in the X-ray complex) and nonspecific association, either taking into account hydrodynamic anisotropy of the proteins or treating them as hydrodynamically equivalent spheres. We found that even relatively small anisotropy of associating proteins may influence the rate of their encounter and this effect is quantitatively measurable in the simulations. The role of the anisotropic diffusion manifests itself only in case of specific encounters while the association toward nonspecific complexes is not influenced by anisotropic diffusion. Association rate constants obtained from Brownian dynamics simulations for the studied system are up to 20% larger when hydrodynamic anisotropies of barnase and barstar are taken into account. Moreover, the dissociation from the specific complex is also accelerated in case of anisotropic diffusion.