Modeling negative ion defect migration through the gramicidin A channel

• Published in: Journal of molecular modeling Vol. 15; no. 8; pp. 1009 - 1012
• Main Authors: Nemukhin, Alexander V, Kaliman, Ilya A, Moskovsky, Alexander A
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.08.2009; Springer-Verlag
• Subjects: Algorithms; Amino Acid Sequence; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Computer Appl. in Life Sciences; Computer Applications in Chemistry; Computer Simulation; gramicidin; Gramicidin - chemistry; Gramicidin - metabolism; Hydrogen Bonding; Kinetics; Membrane Potentials; Models, Chemical; Models, Molecular; Molecular Medicine; Molecular Sequence Data; Original Paper; Potential of mean force; Protein Binding; Protein Structure, Secondary; Protein Structure, Tertiary; Proton transport; Protons; Theoretical and Computational Chemistry; Water - chemistry; Water - metabolism; Potential of mean force; Gramicidin; Proton transport
• DOI: 10.1007/s00894-009-0463-8
• ISSN: 0949-183X; 1610-2940; 0948-5023

The results of potential of mean force (PMF) calculations for the distinct stages of proton conduction through the gramicidin A channel, including proton migration, reorientation of the water file and negative ion defect migration, are presented. The negative ion defect migration mechanism was hypothesized in experimental studies but was not considered previously in molecular dynamics simulations. The model system consisted of the peptide chains constructed on the base of the structure PDBID:1JNO, the inner file of nine water molecules and external clusters of water molecules placed at both ends of the channel. Potential energy functions were computed with the CHARMM/PM6/TIP3P parameters. The results obtained for proton migration and water file reorientation are basically consistent with those reported previously by Pómès and Roux (Biophys J 82:2304, 2002) within the similar approach. For the newly considered mechanism of negative ion defect migration from the channel center to the end of the water file we obtain the energy 3.8 kcal mol⁻¹ which is not considerably different from the activation energy of water reorientation, 5.4 kcal mol⁻¹. Therefore this mechanism may principally compete for the rate-limiting step in proton conduction in gramicidin.