C‑Graphs Tool with Graphical User Interface to Dissect Conserved Hydrogen-Bond Networks: Applications to Visual Rhodopsins

Dynamic hydrogen-bond networks provide
proteins with structural
plasticity required to translate signals such as ligand binding into
a cellular response or to transport ions and larger solutes across
membranes and, thus, are of central interest to understand protein
reaction mechanisms. Here, we present C-Graphs, an efficient tool
with graphical user interface that analyzes data sets of static protein
structures or of independent numerical simulations to identify conserved,
vs unique, hydrogen bonds and hydrogen-bond networks. For static structures,
which may belong to the same protein or to proteins with different
sequences, C-Graphs uses a clustering algorithm to identify sites
of the hydrogen-bond network where waters are conserved among the
structures. Using C-Graphs, we identify an internal protein–water
hydrogen-bond network common to static structures of visual rhodopsins
and adenosine A2A G protein-coupled receptors (GPCRs). Molecular dynamics
simulations of a visual rhodopsin indicate that the conserved hydrogen-bond
network from static structure can recruit dynamic hydrogen bonds and
extend throughout most of the receptor. We release with this work
the code for C-Graphs and its graphical user interface.