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MS2DB+ is an open-source platform-independent web application for determining, in polynomial time, the disulfide linkages in proteins using tandem mass spectrometry (MS/MS) data. It utilizes an efficient approximation algorithm which allows the consideration of multiple ion-types ( a, ao, a*, b, bo, b*, c, x, y, yo, y*, and z ) in the analysis. Once putative disulfide bonds are identified, a graph optimization approach is used to obtain the most likely global disulfide connectivity pattern. Availability-http://haddock2.sfsu.edu/~ms2db/disulfidebond/.