Modeling Flexible Docking of Protein Monomers using Rigid-body Docking along Minimal Energy Paths

Protein-protein interactions are an essential component of biological function and important targets for protein design. When given two separate proteins that do not undergo conformational changes during binding, rigid-body docking and state-of-the-art scoring methods can be used to accurately predict the coordinates of the docked complex. However, most protein complexes undergo significant conformational changes upon binding, dramatically increasing the complexity of the problem. To better understand this ``flexible" docking process, we first generate the minimal energy path between the x-ray crystal structures of the bound and unbound conformations of the protein heterodimers. We will perform rigid-body docking and model scoring for successive conformations along the minimal energy path, which will allow us to assess the magnitude of the root-mean-square deviations in atomic coordinates beyond which it is difficult to predict protein-protein interfaces using the unbound structures.