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Computational prediction of ion permeation characteristics in the glycine receptor modified by photo-sensitive compounds

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Abstract

We conduct computational analyses of ion permeation characteristics in a model glycine receptor (GlyR) modified by photo-sensitive compounds. In particular, we consider hypothetical attachment to the channel of charge-neutral chemical groups which can be photo-activated by shining light of an appropriate wavelength on the system. After illumination, the attached molecules become charged via a photodissociation process or excited into a charge-separated state (thus generating a significant electric dipole). We carry out Brownian Dynamics simulations of ion flow through the channel in the presence of the additional charges generated in this fashion. Based on these calculations, we predict that photo-activation of appropriately positioned photo-sensitive compounds near the channel mouth can significantly modify the rate of ion permeation and the current rectification ratio. Possible implications for GlyR-based device designs are briefly discussed.

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Acknowledgements

We wish to thank S. Essiz for her valuable assistance preparing the figures. We gratefully acknowledge computational support from Center for Molecular and Materials Simulation (CMMS) at the University of Pittsburgh. The work of MHC and RDC was supported in part by NSF Grant No.CHE-0518044 and ARO-MURI Grant No. DADD19-02-1-0227.

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Authors and Affiliations

  1. Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, 15260, USA

    Mary Hongying Cheng & Rob D. Coalson

  2. Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA

    Michael Cascio

  3. Department of Chemistry, Carnegie Mellon University, Pittsburgh, PA, 15260, USA

    Maria Kurnikova

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  1. Mary Hongying Cheng
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  2. Rob D. Coalson
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  3. Michael Cascio
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  4. Maria Kurnikova
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Corresponding author

Correspondence to Rob D. Coalson.

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Cheng, M.H., Coalson, R.D., Cascio, M. et al. Computational prediction of ion permeation characteristics in the glycine receptor modified by photo-sensitive compounds. J Comput Aided Mol Des 22, 563–570 (2008). https://doi.org/10.1007/s10822-008-9200-0

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  • DOI: https://doi.org/10.1007/s10822-008-9200-0

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