Energy landscape analysis of protein dimers

Many cellular functions are carried out by proteins that are bound together in multiprotein complexes. The binding between two highly flexible proteins to form homodimers is studied here using energy landscape theory and simulations based on a perfectly funneled energy landscape. With the aim to survey the range of binding mechanisms, two sets of homodimers were selected based on the experimental knowledge of whether stable monomers are needed for binding to take place. We find that the binding mechanism can be predicted based on the structure of the complex subunits alone. On average, the theory predicts a lower stability for subunits that are less compact and less hydrophobic, indicating, in agreement with their experimental classification, that their folding will be coupled to their binding. On the other hand, when a monomeric intermediate is experimentally found, the predicted stability of the monomers is comparable to that of known folded proteins. Furthermore, when dimerization is coupled to monomer folding, the interface is more hydrophobic.