title: Statistical analysis of ion mobility spectrometry. I. Unbiased and guided replica-exchange molecular dynamics.
abstract: Achieving (bio)macromolecular structural assignment from the interpretation of ion mobility spectrometry (IMS) experiments requires successful comparison with computer modeling. Replica-exchange molecular dynamics simulations with suitable force fields not only offer a convenient framework to locate relevant conformations, especially in the case of multiple-funnel energy landscapes, but they are also well suited to statistical analyses. In the present paper, we discuss two extensions of the method used to improve its efficiency in the context of IMS. Two doubly-protonated polyalanines [RA(4)XA(4)K + 2H](2+) with X=V and D appear as favorable cases for which the calculated collision cross-section distributions naturally agree with the measurements, providing reliable candidate structures. For these compounds, a careful consideration of other order parameters based on the weighted histogram method resolves several otherwise hidden underlying conformational families. In the case of a much larger peptide exhibiting bistability, assignment is more difficult but could be achieved by guiding the sampling with an umbrella potential using the square gyration radius as the biasing coordinate. Applied to triply protonated bradykinine, the two presented methods indicate that different conformations compatible with the measurements are very close in energy.
authors: Université de Lyon, Villeurbanne, France. fabien.chirot@univ-lyon1.fr
authors: Fabien
authors: F
authors: Chirot
authors: Florent
authors: F
authors: Calvo
authors: Florian
authors: F
authors: Albrieux
authors: Jérôme
authors: J
authors: Lemoine
authors: Yury O
authors: YO
authors: Tsybin
authors: Philippe
authors: P
authors: Dugourd
mesh_terms: D007477:Ions / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods*; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D055550:Protein Stability
chemical_list: D007477:Ions; D010455:Peptides; C019529:polyalanine