Proton transfer in bacteriorhodopsin studied with SCC-DFTB QM/MM

Nicoleta Bondar, N.Bondar@dkfz.de1, Marcus Elstner, m.elstner@dkfz.de2, Stefan
Fischer3, Sandor Suhai1, and Jeremy C. Smith3. (1) Computational Molecular
Biophysics, IWR, University of Heidelberg, Im Neuenheimer Feld 368, D-69120
Heidelberg, Germany, (2) Theoretical Chemistry, TU Braunschweig,
Hans-Sommer-Straße 10, 38106 Braunschweig, Germany, (3) IWR - Computational
Molecular Biophysics, University of Heidelberg, Im Neuenheimer Feld 368, 69120
Heidelberg, Germany

Due to uncertainties in the relative orientation of the proton donor (retinal
Schiff base) and acceptor (Asp85) groups, the mechanism of the primary
proton-transfer step in bacteriorhodopsin is highly controversial. To understand
how retinal and protein structural rearrangements translate into proton pumping
we performed an extensive set of Quantum Mechanical/Molecular Mechanical
reaction-path calculations using SCC-DFTB to describe the quantum mechanical
region. Fine-tuning of the retinal chain in the K intermediate allows
bacteriorhodopsin to store energy while avoiding a wasteful thermal relaxation
back to the resting state bR. Although the primary proton-transfer step involves
a short distance (3-4 Å), three very different pathways were found that have
barriers consistent with experiment. The proton-transfer energetics is shaped by
the flexibility and electrostatic environment of the protein, and
hydrogen-bonding interactions between the proton acceptor Asp85 and specific
water molecules significantly influence the stability of the post
proton-transfer state.