Gas phase conformations of biological molecules: The hydrogen/deuterium exchange mechanism

A model was developed to describe the deuterium uptake of gas phase polypep tide ions via H/D exchange with D2O. Ab initio calculations established, fo r energetic reasons, that the exchange must take place via a "relay" mechan ism involving both a charged site and a nearby basic site. Molecular dynami cs simulations indicated that the D2O molecule did not penetrate the core o f the example peptide, protonated bradykinin (Bk+H)(+), and hence the relay mechanism must occur on the peptide surface. Two factors were deemed to be important: (1) The surface accessibility of the charged sites and the basi c sites and (2) the distances between them. An algorithm was developed that accounted for these features using the absolute exchange rate as a free pa rameter. Excellent agreement was obtained with experiment when equal weight was given to an ensemble of low energy conformations of (Bk+H)(+), assumed to have a salt bridge primary structure. Single conformations, or other pr otonated forms, did not allow,good a,agreement with experiment for any valu e of the absolute exchange rate constant. (J Am Soc Mass Spectrom 1999, 10, 9-14) (C) 1999 American Society for Mass Spectrometry.