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Diffusion of Glycerol through Escherichia coli Aquaglyceroporin GlpF

Jérôme Hénin ^*, Emad Tajkhorshid , Klaus Schulten  and Christophe Chipot ^*

^* Equipe de Dynamique des Assemblages Membranaires, UMR Centre National de la Recherche Scientifique/UHP 7565, Nancy Université BP 239, Nancy, France; and Theoretical and Computational Biophysics Group, Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois

Correspondence: Address reprint requests to Christophe Chipot, E-mail: christophe.chipot{at}edam.uhp-nancy.fr; or Klaus Schulten, E-mail: kschulte{at}ks.uiuc.edu.

The glycerol uptake facilitator, GlpF, a major intrinsic protein found in Escherichia coli, selectively conducts water and glycerol across the inner membrane. The free energy landscape characterizing the assisted transport of glycerol by this homotetrameric aquaglyceroporin has been explored by means of equilibrium molecular dynamics over a timescale spanning 0.12 µs. To overcome the free energy barriers of the conduction pathway, an adaptive biasing force is applied to the glycerol molecule confined in each of the four channels. The results illuminate the critical role played by intramolecular relaxation on the diffusion properties of the permeant. These free energy calculations reveal that glycerol tumbles and isomerizes on a timescale comparable to that spanned by its adaptive-biasing-force-assisted conduction in GlpF. As a result, reorientation and conformational equilibrium of glycerol in GlpF constitute a bottleneck in the molecular simulations of the permeation event. A profile characterizing the position-dependent diffusion of the permeant has been determined, allowing reaction rate theory to be applied for investigating conduction kinetics based on the measured free energy landscape.