Structural preferences of gas-phase M2TMP monomers upon sequence variations.

The conformations of a number of M2TMP(22-46) sequence variants have been investigated using ion mobility spectrometry (IMS). Substantial conformational changes were evidenced by IMS upon the variation of a single amino acid in the peptide sequence, with two main drift time signatures. Replica-exchange molecular dynamics simulations were used to help assign the structures of the different identified conformers. Even though one-on-one agreement with experiment was found for only two variants, the simulations generally confirmed the existence of two structural families. Based on these results, most of the triply protonated variants, including the wild-type peptide, were found to display collision cross sections in agreement with compact conformations in the gas phase, whereas they tend to form extended α-helices in the condensed phase, as confirmed by circular dichroism and previously reported NMR measurements. The destabilization of α-helices in vacuo upon amino acid substitution is interpreted as being driven by the solvation pattern of the charges.