Effects of frustration, confinement, and surface interactions on the dimerization of an off-lattice beta-barrel protein.

We study the effects of confinement, sequence frustration, and surface interactions on the thermodynamics of dimerization of an off-lattice minimalist beta-barrel protein using replica exchange molecular dynamics. We vary the degree of frustration of the protein by tuning the specificity of the hydrophobic interactions and investigate dimerization in confining spheres of different radii. We also investigate surface effects by tethering the first residue of one of the proteins to a uniformly repulsive surface. We find that increasing the confinement and frustration stabilize the dimer, while adding a repulsive surface decreases its stability. Different ensembles of structures, including properly dimerized and various partially dimerized states, are observed at the association transition temperature T(a), depending on the amount of frustration and whether a surface is present. The presence of a surface is predicted to alter the morphology of larger aggregates formed from partially unfolded dimeric conformations.