Active site structure and absorption spectrum of channelrhodopsin-2 wild-type and C128T mutant

Chemical Science
Yanan GuoMarcus Elstner

Abstract

In spite of considerable interest, the active site of channelrhodopsin still lacks a detailed atomistic description, the understanding of which could strongly enhance the development of novel optogenetics tools. We present a computational study combining different state-of-the-art techniques, including hybrid quantum mechanics/molecular mechanics schemes and high-level quantum chemical methods, to properly describe the hydrogen-bonding pattern between the retinal chromophore and its counterions in channelrhodopsin-2 Wild-Type and C128T mutant. Especially, we show by extensive ground state dynamics that the active site, containing a glutamic acid (E123) and a water molecule, is highly dynamic, sampling three different hydrogen-bonding patterns. This results in a broad absorption spectrum that is representative of the different structural motifs found. A comparison with bacteriorhodopsin, characterized by a pentagonal hydrogen-bonded active site structure, elucidates their different absorption properties.

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Citations

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Methods Mentioned

BETA
NMR
X-ray

Software Mentioned

MM
SORCI
DFTB
OM2
MNDO2005
GROMACS
CHARMM37b1
MRCI
ORCA
MMTSB

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