A novel projection approximation algorithm for the fast and accurate computation of molecular collision cross sections (IV). Application to polypeptides

One fundamental problem of IMS-MS based structure elucidation is achieving agreement between experimental cross sections and those predicted by theoretical algorithms for candidate structures for the compound of interest. Recently, the projected superposition approximation (PSA) was introduced specifically to yield accurate ion mobility cross sections for complex macroscopic systems with great computational efficiency. Here, the PSA method is shown to give cross sections within experimental error over an extended temperature range for short peptide sequences of unknown structure. The method is robust for structures derived from different levels of theory. The existing trajectory method (TJM) and projection approximation (PA) method were shown sensitive to the level of theory used to derive the candidate structures. The PSA method is much faster than the TJM for the systems measured here. As ion mobility instrumentation improves and becomes increasingly available, cross section measurements and theoretical modeling can become a routine technique for determination of macromolecular structure under a variety of experimental conditions, given the accuracy of the PSA method. (C) 2013 Elsevier B.V. All rights reserved.