  High-resolution structural information on membrane proteins is essential for
understanding cell biology and for structure-based design of new medical drugs
and drug delivery strategies. X-ray diffraction (XRD) can provide
{\AA}ngstrom-level information about the structure of membrane proteins.
Ideally protein structures should be solved in environments as close to the
original biological context as possible. However, it is virtually impossible to
crystallize proteins within the complex environment of a biological membrane.
Instead, membrane proteins are typically transferred from their native membrane
environment into detergent micelles, chemically stabilized and crystallized,
all of which can compromise the conformation. This makes it imperative to
develop alternative high-resolution techniques which are compatible with
biological conditions. Here, we describe how a combina-tion of
surface-sensitive vibrational spectroscopy in model membranes and molecular
dynamics simulations can account for the native membrane environment. We
observe the structure of glycerol facilitator channel (GlpF), an aquaporin
membrane channel finely tuned to selectively transport water and glycerol
molecules across the membrane barrier. We find subtle but significant
differences between the XRD structure and the in-ferred in situ structure of
GlpF.
