• molecular recognition;
  • amide hydrogen exchange;
  • protein–protein docking


The macromolecular docking problem that must be solved for experimental biologists is prediction of the structures of complexes for which the components are known or reliably modeled in the unbound state, but the structure of the complex is unknown. The current state of the art in macromolecular docking is such that solving this problem usually requires supplementary experimental chemical and/or biological information to evaluate computational predictions. Amide 1H/2H exchange measured by mass spectroscopy is a promising approach for obtaining such information, because it can reveal interfacial regions of each member of the complex and identify regions of conformational flexibility in the structure. In a previous article (Anand et al., Proc Natl Acad Sci USA 2003;100:13264–13269), we used 1H/2H exchange data to predict the structure of a complex between regulatory and catalytic subunits of protein kinase A. Comparison of the prediction with a recent crystal structure determination (Kim et al., Science 2005;307:690–696) showed large conformational change in the regulatory subunit on formation of the complex. Analysis of the prediction, previous CAPRI results, novel data processing methods for the 1H/2H exchange data, and new fragment docking computations give grounds for cautious optimism that this method can be useful even in cases of substantial conformational change. Proteins 2005;60:302–307. © 2005 Wiley-Liss, Inc.