How alkali metal ion binding alters the conformation preferences of gramicidin A: a molecular dynamics and ion mobility study

Here, we present a systematic study combing electrospray ionization-ion mobility experiments and an enhanced sampling molecular dynamics, specifically integrated tempering sampling molecular dynamics simulations (ITS-MDS), to explore the conformations of alkali metal ion (Na, K, and Cs) adducts of gramicidin A (GA) in vacuo. Folding simulation is performed to obtain inherent conformational preferences of neutral GA to provide insights about how the binding of metal ions influences the intrinsic conformations of GA. The comparison between conformations of neutral GA and alkali metal ion adducts reveals a high degree of structural similarity, especially between neutral GA and GA + Na](+); however, the structural similarities decrease as ionic radius of the metal increases. Collision cross section (CCS) profiles for GA + Na](+) and GA + Cs](+) ions obtained from by ITS-MDS compare favorably with the experimental CCS, but there are significant differences from CCS profiles for GA + K](+) ions. Such discrepancies between the calculated and measured CCS profiles for GA + K](+) are discussed in terms of limitations in the simulation force field as well as possible size-dependent coordination of the GA + K](+) ion complex.