Jeremiah Tipton - Computing H/D-Exchange Rates of Single Residues from Data of Proteolytic Fragments

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  Publication Details (including relevant citation   information):

  Althaus, E.; Canzar, S.; Ehrler, C.; Emmett, M.R.; Karrenbauer,   A.; Marshall, A.G.; Meyer-Base, A.; Tipton,   J.D.; Zhang, H.M. BMC Bioinformatics, 11 (11),   424, (2010)



  Protein conformation and protein/protein interaction can be   elucidated by solution-phase Hydrogen/Deuterium exchange (sHDX)   coupled to high-resolution mass analysis of the digested protein   or protein complex. In sHDX experiments mutant proteins are   compared to wild-type proteins or a ligand is added to the   protein and compared to the wild-type protein (or mutant). The   number of deuteriums incorporated into the polypeptides generated   from the protease digest of the protein is related to the solvent   accessibility of amide protons within the original protein   construct.



    In this work, sHDX data was collected on a 14.5 T FT-ICR MS. An     algorithm was developed based on combinatorial optimization     that predicts deuterium exchange with high spatial resolution     based on the sHDX data of overlapping proteolytic fragments.     Often the algorithm assigns deuterium exchange with single     residue resolution.  



    With our new method it is possible to automatically determine     deuterium exchange with higher spatial resolution than the     level of digested fragments.  

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