ClusPro-DC: Dimer Classification by the Cluspro Server for Protein–Protein Docking

• The X-ray structure of a protein does not determine its oligomeric state in solution.
• The oligomeric state can be determined by exhaustively sampling the free energy landscape.
• The method provides information complementary to PISA and EPPIC, improving accuracy.
• Dimer classification is a new option in the ClusPro protein–protein docking server.

ClusPro-DC (https://cluspro.bu.edu/) implements a straightforward approach to the discrimination between crystallographic and biological dimers by docking the two subunits to exhaustively sample the interaction energy landscape. If a substantial number of low energy docked poses cluster in a narrow vicinity of the native structure of the dimer, then one can assume that there is a well-defined free energy well around the native state, which makes the interaction stable. In contrast, if the interaction sites in the docked poses do not form a large enough cluster around the native structure, then it is unlikely that the subunits form a stable biological dimer. The number of near-native structures is used to estimate the probability of a dimer being biological. Currently, the server examines only the stability of a given interface rather than generating all putative quaternary structures as accomplished by PISA or EPPIC, but it complements the information provided by these methods.

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