Combining ion mobility mass spectrometry and infrared multiphoton dissociation spectroscopy to probe the structure of gas-phase vancomycin–Ac2LKDADA non-covalent complex

The structure of doubly protonated vancomycin antibiotics with its cell-wall precursor analogue Ac2LKDADA has been investigated in the gas phase through a combined laser spectroscopy, ion mobility and theoretical modeling approach. Replica-exchange molecular dynamics simulations using the Amber99 force field were performed to explore the potential energy landscape of isolated vancomycin ions, as well as the different binding sites with the receptor. Among the low-energy conformers found, those with a calculated diffusion cross-section consistent with ion mobility experiments were selected for further optimization, and their IR spectra were simulated using a hybrid quantum mechanics/semi-empirical (QM/SE) method at the DFT/B3LYP/6-31g(d):AM1 level. Both theoretical and experimental findings provide strong evidence that the native structure of the complex is not preserved in vacuo for the doubly protonated species.

Graphical abstractThe structure of doubly protonated vancomycin antibiotics with its cell-wall precursor analogue Ac2LKDADA has been investigated in the gas phase through a combined laser spectroscopy, ion mobility and theoretical modeling approach.Figure optionsDownload full-size imageDownload high-quality image (91 K)Download as PowerPoint slide