GalaxyDomDock: protein domain structure assembly by docking

Protein domains are evolutionarily and functionally independent protein structure units, and domain-domain interactions may be related to protein functions. Predicting assembled domain structures is thus an important part of protein structure prediction.  Ab initio structure assembly of domains is needed when each domain structure can be predicted reliably but there are no proper structure templates covering the whole protein. In this research, we have developed a domain assembly method called GalaxyDomDock that predicts the relative orientation of two domains. Based on the analysis that the inter-domain interactions and the inter-chain interactions are similar, we decided to apply an  ab initio protein-protein docking method, GalaxyTongDock, for the domain assembly problem. First, in GalaxyDomDock, up to 10,000 assembled domain structures were predicted by GalaxyTongDock with additional geometric consideration of the domain linker which effectively reduces the conformational space for docking. The predicted structures were further screened for domain connectabiliy by the given linker using Dijkstra’s algorithm. Lastly, structural redundancy of the remaining structures was removed by clustering dependent on the protein size. GalaxyDomDock showed better or comparable performance compared to AIDA and Rosetta domain assembly protocols on various categories of benchmark tests.