Proton Transfers to DNA in Native Electrospray Ionization Mass Spectrometry: A QM/MM Study

Abstract

ABSTRACTNative electrospray ionization - ion mobility mass spectrometry (N-ESI/IM-MS) is a powerful approach for low-resolution structural studies of DNAs in the free state and in complex with ligands. Solvent vaporization is coupled with proton transfers from ammonium ions to the DNA resulting in a reduction of the DNA charge. Here we provide insight on these processes by classical MD and QM/MM free energy calculations on the (GpCpGpApApGpC) heptamer, for which a wealth of experiments is available. Our multiscale simulations, consistent with experimental data, reveal a highly complex scenario: the proton either sits on one of the molecules or is fully delocalized on both, depending on the level of hydration of the analytes and on size of the droplets formed during the electrospray experiments. This work complements our previous study on theintramolecularproton transfer on the same heptamer occurring after the processes studied here, and, together, provide a first molecular view of proton transfer in N-ESI/IM-MS.TOC GRAPHICS