  Revealing the structure of complex biological macromolecules, such as
proteins, is an essential step for understanding the chemical mechanisms that
determine the diversity of their functions. Synchrotron based x-ray
crystallography and cryo-electron microscopy have made major contributions in
determining thousands of protein structures even from micro-sized crystals.
They suffer from some limitations that have not been overcome, such as
radiation damage, the natural inability to crystallize of a number of proteins
and experimental conditions for structure determination that are incompatible
with the physiological environment. Today the ultrashort and ultra-bright
pulses of X-ray free-electron lasers (XFELs) have made attainable the dream to
determine protein structure before radiation damage starts to destroy the
samples. However, the signal-to-noise ratio remains a great challenge to obtain
usable diffraction patterns from a single protein molecule. We describe here a
new methodology that should overcome the signal and protein crystallization
limits. Using a multidisciplinary approach, we propose to create a two
dimensional protein array with defined orientation attached on a
self-assembled-monolayer. We develop a literature-based, flexible toolbox
capable of assembling different proteins on a functionalized surface while
keeping them under physiological conditions during the experiment, using a
water-confining graphene cover.
