Bridge: A Graph-Based Algorithm to Analyze Dynamic H‑Bond Networks in Membrane Proteins

Membrane
proteins that function as transporters or receptors must
communicate with both sides of the lipid bilayer in which they sit.
This long distance communication enables transporters to move protons
or other ions and small molecules across the bilayer and receptors
to transmit an external signal to the cell. Hydrogen bonds, hydrogen-bond
networks, and lipid–protein interactions are essential for
the motions and functioning of the membrane protein and, consequently,
of outmost interest to structural biology and numerical simulations.
We present here Bridge, an algorithm tailored for efficient analyses
of hydrogen-bond networks in membrane transporter and receptor proteins.
For channelrhodopsin, a membrane protein whose functioning involves
proton-transfer reactions, Bridge identifies extensive networks of
protein–water hydrogen bonds and an unanticipated network that
can bridge transiently two proton donors across a distance of ∼20
Å. Graphs of the protein hydrogen bonds reveal rapid propagation
of structural changes within hydrogen-bond networks of mutant transporters
and identify protein groups potentially important for the proton transfer
activity. The algorithm is made available as a plugin for PyMol.