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Coupled Dynamics & Protein Function

Recent findings on the role of environmental vibrations in the observation of long-lived quantum coherences in energy transfer in the photosynthetic system point towards a more general realization that under certain biological conditions thermal environmental vibrations cannot be modeled as white noise. Vibrational correlations and coherences that arise due to structural constrains and system-bath coupling, could lead to stochastic resonances, non-Markovian dynamics or colored noise which may all contribute functionally beyond the context of quantum coherent energy transfer to the bio-molecular function at different scales.

Potasium channel size and localization in a bacterial cell
Fig. 1: Potassium channel size and location in a bacterial cell. (click image for details)

We are investigating these general questions on the example of ion selectivity and transport in potassium channels. We are interested in understanding how the dynamic interactions in the selectivity filter are responsible for the observed high ion selectivity and transport rates and the possible functional role of coherent vibrational modes in this context.

Fig. 2: Schematic illustration of the KcsA potassium channel.
Fig. 2: Schematic illustration of the KcsA potassium channel (Click image for details).

Most of our today’s understanding on the function of channels is based on static crystallography data and electrophysiology. However, it is increasingly believed that in order to fully understand the mechanism that lead to the extreme ion selectivity and transport properties of ion channels, one has to account the fast dynamics of the system on the atomic scales. To investigate these ideas, we are studying the dynamics of the selectivity filter using time resolved spectroscopy in the IR regime. Our goal is to experimentally identify the signatures of the transient interactions of K+ with binding sites of the selectivity filter during ion conduction and potential couplings that might lead to vibrational coherences. Spectroscopic techniques such as Two-dimensional Infrared Spectroscopy (2DIR) provide the necessary time resolution to observe such coherences.
We have recently shown that spectroscopic signatures due to carbonyl – potassium interaction, as they would arise during transient interactions of potassium ions with the selectivity can be resolved in model molecules that mimic different potassium – carbonyl coordination states in the selectivity filter (Fig. 3). The frequency red-shifting and diagonal narrowing of the 2DIR line-shapes upon K+-binding to the model molecules show the induced ordering and changes in the electrostatic environment and

Fig. 3: FTIR, Raman and 2DIR spectroscopy on model compounds
Fig. 3: FTIR, Raman and 2DIR spectroscopy on model compounds (Click image for details).

suggest that similar effects can be expected in the selectivity filter of KcsA.In order to apply this tool to a trans-membrane protein such the KcsA it is necessary to single out the carbonyl groups of interest by introducing site specific isotope labels. Using molecular dynamic-based simulations of the FTIR and 2DIR spectra of the entire KcsA complex we found that by combing isotope labeling with 2DIR spectroscopy, the signatures of K+ interaction with individual binding sites would be experimentally observable in KcsA. Modeling of all possible isotope label combinations of the selectivity filter identified specific labeling combinations that would maximize our expected experimental signatures (Fig. 4).

Fig. 4: Calculation of 2DIR spectra off KcsA. (click image for details)

We are currently in the process of producing such isotope labeled samples for our 2D-IR experiments and evaluating different strategies which should ultimately allow us to perform transient 2D-IR experiments. We are complementing the above approach based on 2D-IR spectroscopy with advanced schemes for electrophysiology.

Relevant publications:

Z. Ganim, A. Tokmakoff and A. Vaziri (2011), Vibrational excitons in ionophores; Experimental  probes for quantum coherence-assisted ion transport and selectivity in ion channels, New J. Phys. (2013)  (Download)

Vaziri A., Plenio M. (2010). Quantum coherence in ion channels: resonances, transport and verification, New Journal of Physics (2012) (Download)