The ClusPro web server is a widely used tool for protein-protein docking, offering both basic and advanced options. Basic use requires only two files in Protein Data Bank format, while advanced options include removing unstructured regions, applying attraction or repulsion, accounting for pairwise distance restraints, constructing homo-multimers, considering small-angle X-ray scattering (SAXS) data, and finding heparin binding sites. Six different energy functions are available, and each energy parameter set results in ten models defined by centers of highly populated clusters of low-energy docked structures. The protocol describes the use of various options, construction of auxiliary restraint files, selection of energy parameters, and analysis of results. Despite its heavy usage, runs are typically completed in less than 4 hours. ClusPro has been extensively validated and has consistently been the best automated server in the CAPRI challenge, demonstrating its effectiveness in predicting protein-protein interactions. However, it has limitations, such as the inability to handle flexible peptides, non-standard amino acids, and complex multimers. The server is available for use without registration, but results are publicly accessible.The ClusPro web server is a widely used tool for protein-protein docking, offering both basic and advanced options. Basic use requires only two files in Protein Data Bank format, while advanced options include removing unstructured regions, applying attraction or repulsion, accounting for pairwise distance restraints, constructing homo-multimers, considering small-angle X-ray scattering (SAXS) data, and finding heparin binding sites. Six different energy functions are available, and each energy parameter set results in ten models defined by centers of highly populated clusters of low-energy docked structures. The protocol describes the use of various options, construction of auxiliary restraint files, selection of energy parameters, and analysis of results. Despite its heavy usage, runs are typically completed in less than 4 hours. ClusPro has been extensively validated and has consistently been the best automated server in the CAPRI challenge, demonstrating its effectiveness in predicting protein-protein interactions. However, it has limitations, such as the inability to handle flexible peptides, non-standard amino acids, and complex multimers. The server is available for use without registration, but results are publicly accessible.