Chloride ion conduction without water coordination in the pore of ClC protein

• Published in: Journal of computational chemistry Vol. 31; no. 3; pp. 603 - 611
• Main Authors: Ko, Youn Jo, Jo, Won Ho
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.02.2010; Wiley Subscription Services, Inc
• Subjects: Algorithms; Atoms & subatomic particles; Chloride Channels - chemistry; Chloride Channels - metabolism; chloride ion conduction; Chlorides - chemistry; Chlorides - metabolism; ClC channel; Escherichia coli - chemistry; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - metabolism; Glutamates - chemistry; Hydrochloric acid; Hydrogen - chemistry; Hydrophobic and Hydrophilic Interactions; ion channel; Ion Channel Gating; membrane protein; Molecular Dynamics Simulation; Molecules; Permeability; Porosity; Proteins; Protons; Simulation; Thermodynamics; Water - chemistry
• ISSN: 0192-8651; 1096-987X
• DOI: 10.1002/jcc.21432

In the present work, we have found by an atomistic molecular dynamics simulation that hydrogen atoms originating from the residues of a prokaryotic ClC protein (EcClC) stabilize the chloride ion without water molecules in the pore of ClC protein. When the chloride ion conduction is simulated by pulling a chloride ion along the pore axis, the free energy barrier for chloride ion conduction is calculated to be low (4 kcal/mol), although the chloride ion is stripped of its hydration shell as it passes through the dehydrated pore region. The calculation of the number of hydrogen atoms surrounding the chloride ion reveals that water molecules hydrating the chloride ion are replaced by polar and non-polar hydrogen atoms protruding from the protein residues. From the analysis of the pair interaction energy between the chloride ion and these hydrogen atoms, it is realized that the hydrogen atoms from the protein residues stabilize the chloride ion at the dehydrated region instead of water molecules, by which the energetic penalty for detaching water molecules from the permeating ion is compensated.