GalaxyHeteromer: protein heterodimer structure prediction by template-based and ab initio docking

Abstract

Abstract 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.