Predicting Protein Dimer Structures Using MELD × MD

It is challenging to predict the docked conformations of two proteins. Current methods are susceptible to errors from treating proteins as rigid bodies and from an inability to compute relative Boltzmann populations of different docked conformations. Here, we show that by using the ClusPro server as a front end to generate possible protein-protein contacts, and using Modeling Employing Limited Data (MELD) accelerated molecular dynamics (MELD × MD) as a back end for atomistic simulations, we can find 16/20 native dimer structures of small proteins as those having the lowest free energy, starting from good-bound-backbone structures. We show that atomistic MD free energies can be used to identify native protein dimer structures.