GalaxyDomDock: An Ab Initio Domain–domain Docking Web Server for Multi-domain Protein Structure Prediction.

[Display omitted] • Domain–domain docking can provide useful information when it is difficult to predict complete multidomain protein structures accurately and/or when multiple conformational states with different domain orientations are present. • GalaxyDomDock is an ab initio domain–domain docking web server that returns possible docked conformations of two given domain structures without relying on the availability of known structures or sequences of related proteins. • GalaxyDomDock utilizes an energy-based protein–protein docking method for initial sampling of possible domain orientations, Dijkstra's algorithm to filter out geometrically infeasible orientations for the given linker, and FALC loop sampling method for linker structure modeling. • GalaxyDomDock exhibits better performance than existing ab initio domain–domain docking methods such as AIDA and Rosetta. A significant proportion of proteins comprise multiple domains. Domain–domain docking is a tool that predicts multi-domain protein structures when individual domain structures can be accurately predicted but when domain orientations cannot be predicted accurately. GalaxyDomDock predicts an ensemble of domain orientations from given domain structures by docking. Such information would also be beneficial in elucidating the functions of proteins that have multiple states with different domain orientations. GalaxyDomDock is an ab initio domain–domain docking method based on GalaxyTongDock, a previously developed protein–protein docking method. Infeasible domain orientations for the given linker are effectively screened out from the docked conformations by a geometric filter, using the Dijkstra algorithm. In addition, domain linker conformations are predicted by adopting a loop sampling method FALC. The proposed GalaxyDomDock outperformed existing ab initio domain–domain docking methods, such as AIDA and Rosetta, in performance tests on the Rosetta benchmark set of two-domain proteins. GalaxyDomDock also performed better than or comparable to AIDA on the AIDA benchmark set of two-domain proteins and two-domain proteins containing discontinuous domains, including the benchmark set in which each domain of the set was modeled by the recent version of AlphaFold. The GalaxyDomDock web server is freely available as a part of GalaxyWEB at http://galaxy.seoklab.org/domdock. [ABSTRACT FROM AUTHOR]