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Protein-protein interactions play crucial roles in diverse biological processes, including various disease progressions. Atomistic structural details of protein-protein interactions may provide important information that can facilitate the design of therapeutic agents. GalaxyHeteromer is a freely available automatic web server (http://galaxy.seoklab.org/heteromer) that predicts protein heterodimer complex structures from two subunit protein sequences or structures. When subunit structures are unavailable, they are predicted by template- or distance-prediction-based modelling methods. Heterodimer complex structures can be predicted by both template-based and ab initio docking, depending on the template's availability. Structural templates are detected from the protein structure database based on both the sequence and structure similarities. The templates for heterodimers may be selected from monomer and homo-oligomer structures, as well as from hetero-oligomers, owing to the evolutionary relationships of heterodimers with domains of monomers or subunits of homo-oligomers. In addition, the server employs one of the best ab initio docking methods when heterodimer templates are unavailable. The multiple heterodimer structure models and the associated scores, which are provided by the web server, may be further examined by user to test or develop functional hypotheses or to design new functional molecules., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

We participated in CARPI rounds 38-45 both as a server predictor and a human predictor. These CAPRI rounds provided excellent opportunities for testing prediction methods for three classes of protein interactions, that is, protein-protein, protein-peptide, and protein-oligosaccharide interactions. Both template-based methods (GalaxyTBM for monomer protein, GalaxyHomomer for homo-oligomer protein, GalaxyPepDock for protein-peptide complex) and ab initio docking methods (GalaxyTongDock and GalaxyPPDock for protein oligomer, GalaxyPepDock-ab-initio for protein-peptide complex, GalaxyDock2 and Galaxy7TM for protein-oligosaccharide complex) have been tested. Template-based methods depend heavily on the availability of proper templates and template-target similarity, and template-target difference is responsible for inaccuracy of template-based models. Inaccurate template-based models could be improved by our structure refinement and loop modeling methods based on physics-based energy optimization (GalaxyRefineComplex and GalaxyLoop) for several CAPRI targets. Current ab initio docking methods require accurate protein structures as input. Small conformational changes from input structure could be accounted for by our docking methods, producing one of the best models for several CAPRI targets. However, predicting large conformational changes involving protein backbone is still challenging, and full exploration of physics-based methods for such problems is still to come., (© 2019 Wiley Periodicals, Inc.)

Cellular processes, such as metabolism, signal transduction, or immunity, often depend on the homo-oligomerization of proteins. Detailed structural knowledge of the homo-oligomer structure is therefore crucial for molecular-level understanding of protein functions and their regulation. In this chapter, we introduce the GalaxyHomomer server, which supports easy-to-use web interfaces for general users. It is freely accessible at http://galaxy.seoklab.org/homomer . GalaxyHomomer carries out template-based modeling, ab initio docking or both depending on the availability of proper oligomer templates. It also incorporates recently developed model refinement methods that can consistently improve model quality by performing symmetric loop modeling and overall structure refinement. Moreover, the server provides additional options that can be chosen by the user depending on the availability of information on the monomer structure, oligomeric state, and locations of unreliable/flexible loops or termini.

Protein-protein docking methods are spotlighted for their roles in providing insights into protein-protein interactions in the absence of full structural information by experiment. GalaxyTongDock is an ab initio protein-protein docking web server that performs rigid-body docking just like ZDOCK but with improved energy parameters. The energy parameters were trained by iterative docking and parameter search so that more native-like structures are selected as top rankers. GalaxyTongDock performs asymmetric docking of two different proteins (GalaxyTongDock_A) and symmetric docking of homo-oligomeric proteins with C n and D n symmetries (GalaxyTongDock_C and GalaxyTongDock_D). Performance tests on an unbound docking benchmark set for asymmetric docking and a model docking benchmark set for symmetric docking showed that GalaxyTongDock is better or comparable to other state-of-the-art methods. Experimental and/or evolutionary information on binding interfaces can be easily incorporated by using block and interface options. GalaxyTongDock web server is freely available at http://galaxy.seoklab.org/tongdock. © 2019 Wiley Periodicals, Inc., (© 2019 Wiley Periodicals, Inc.)

Homo-oligomerization of proteins is abundant in nature, and is often intimately related with the physiological functions of proteins, such as in metabolism, signal transduction or immunity. Information on the homo-oligomer structure is therefore important to obtain a molecular-level understanding of protein functions and their regulation. Currently available web servers predict protein homo-oligomer structures either by template-based modeling using homo-oligomer templates selected from the protein structure database or by ab initio docking of monomer structures resolved by experiment or predicted by computation. The GalaxyHomomer server, freely accessible at http://galaxy.seoklab.org/homomer, carries out template-based modeling, ab initio docking or both depending on the availability of proper oligomer templates. It also incorporates recently developed model refinement methods that can consistently improve model quality. Moreover, the server provides additional options that can be chosen by the user depending on the availability of information on the monomer structure, oligomeric state and locations of unreliable/flexible loops or termini. The performance of the server was better than or comparable to that of other available methods when tested on benchmark sets and in a recent CASP performed in a blind fashion., (© The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.)