I-TASSER (Iterative Threading ASSembly Refinement) is a composite pipeline for protein structure prediction and structure-based protein function annotation. Starting from sequence of a target protein, structure templates are identified by threading from the PDB. Full-length target structure is then constructed by fragment re-assembly simulation. The final structure model is further compared to entries in BioLiP structure-function database for biological function interference. Recently, I-TASSER is implemented as an XSEDE science gateway, which helped >14,000 users to decipher structure and function of >38,000 proteins in the last 12 months. The I-TASSER gateway is available at http://zhanglab.ccmb.med.umich.edu/I-TASSER/.