Statistical analysis of ion mobility spectrometry. II. adaptively biased methods, shape correlations

摘要

Following a recent effort [J. Am. Soc. Mass Spectrom. 23, 386-396 (2012)], we continue to explore computational methodologies for generating molecular conformations to support collisional cross sections suggested by ion mobility measurements. Here, adaptively biased molecular dynamics (ABMD) simulations are used to sample the configuration space, to achieve flat-histogram sampling along the reaction coordinates of the first two moments of the gyration tensor. The method is tested, compared with replica-exchange simulations on triplyprotonated bradykinin, on a larger 25-residue peptide. It is found to have a much higher efficiency for producing large sets of conformations in a broad range of diffusion cross-sections, whereas it does not compete with conventional replica-exchange molecular dynamics in locating the lowest-energy structure. Nevertheless, the broad sampling obtained from the ABMD method allows to quantitatively correlate the diffusion cross-section Ω with other geometric order parameters that have simpler interpretation. The strong correlations found between the diffusion cross-section, the radius of gyration, the surface area, the volume of the convex hull suggest an optimal template for accurately mimicking the variations of Ω in a broad range of conformations, using only geometrical information, doing so at a very moderate computational cost. The existence of such a correlation is confirmed on the much larger protein a-lactalbumin.