BIOPHYSICAL THEORY AND MODELING |
Energetics of ion permeation, rejection, binding and block in gramicidin A from free energy simulations
Turgut Bastug 1 and Serdar Kuyucak 1*
1 University of Sydney
* To whom correspondence should be addressed. E-mail: serdar{at}physics.usyd.edu.au.
Submitted on September 16, 2005
Revised on October 27, 2005
Accepted on 15 February 2006
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Abstract |
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The rigid force fields currently used in molecular dynamics (MD) simulations of biomolecules are optimized for globular proteins. Whether they can also be used in MD simulations of membrane proteins is an important issue that needs to be resolved. Here we address this issue using the gramicidin A channel, which provides an ideal test case because of the simplicity of its structure and the availability of a wealth of functional data. Permeation properties of gramicidin A can be summarized as "it conducts monovalent cations, rejects anions and binds divalent cations". Hence a comprehensive test should consider the energetics of permeation for all three types of ions. To that end we construct the potential of mean force for K+, Cl- and Ca2+ ions along the channel axis. For independent confirmation of the results, we also calculate the free energy differences for these ions at the channel center and binding site. We find that "rejection of anions" is satisfied but there are difficulties in accommodating the other two properties using the current MD force fields.
Key Words:
free energy calculations, ion channels, ion permeation and block, molecular dynamics force fields, potential of mean force
