Computing H/D-Exchange rates of single residues from data of proteolytic fragments

BMC Bioinformatics

Methodology Article

Stefan Canzar¹  Carsten Ehrler²  Anke Meyer-Bäse³  Ernst Althaus⁴  Andreas Karrenbauer⁵  Jeremiah D Tipton⁶  Hui-Min Zhang⁶  Alan G Marshall⁷  Mark R Emmett⁷ 

[1] Algorithmic Computational Biology, Centrum Wiskunde & Informatica, Amsterdam, The Netherlands;Center for Bioinformatics, Computer Science Department, Saarland University, 66041, Saarbrücken, Germany;Department of Scientific Computing, Florida State University, 32306-4120, Tallahassee, FL, USA;Institut für Informatik, Fachbereich 08, Staudingerweg 9, 55099, Mainz, Germany;Institute of Mathematics, EPFL, Station 8, 1015, Lausanne, Switzerland;Ion Cyclotron Resonance Program, National High Magnetic Field Laboratory, Florida State University, 1800 East Paul Dirac Drive, 32310-4005, Tallahassee, FL, USA;Ion Cyclotron Resonance Program, National High Magnetic Field Laboratory, Florida State University, 1800 East Paul Dirac Drive, 32310-4005, Tallahassee, FL, USA;Department of Chemistry & Biochemistry, Florida State University, 95 Chieftain Way, 32306, Tallahassee, FL, USA;

关键词: Exchange Rate;    Deuterium;    FK506;    Integer Linear Program;    Deuterium Exchange;   

DOI  :  10.1186/1471-2105-11-424

 received in 2009-01-16, accepted in 2010-08-11,  发布年份 2010

来源: Springer

【 摘 要 】

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

【 授权许可】

CC BY   
© Althaus et al; licensee BioMed Central Ltd. 2010