Stability of an Ion Channel in Lipid Bilayers: Implicit Solvent Model Calculations with Gramicidin
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- 作者：Sharron Bransburg-Zabary ; Amit Kessel ; Menachem Gutman ; and Nir Ben-Tal
- 刊名：Biochemistry
- 出版年：2002
- 出版时间：June 4, 2002
- 年：2002
- 卷：41
- 期：22
- 页码：6946 - 6954
- 全文大小：300K
- 年卷期：v.41,no.22(June 4, 2002)
- ISSN：1520-4995
文摘
Gramicidin is a helical peptide, 15 residues in length, which dimerizes to form ion-conductingchannels in lipid bilayers. Here we report calculations of its free energy of transfer from the aqueousphase into bilayers of different widths. The electrostatic and nonpolar contributions to the desolvationfree energy were calculated using implicit solvent models, in which gramicidin was described in atomicdetail and the hydrocarbon region of the membrane was described as a slab of hydrophobic mediumembedded in water. The free energy penalties from the lipid perturbation and membrane deformationeffects, and the entropy loss associated with gramicidin immobilization in the bilayer, were estimatedfrom a statistical thermodynamic model of the bilayer. The calculations were carried out using two classesof experimentally observed conformations: a head-to-head dimer of two single-stranded (SS) 
-helicesand a double-stranded (DS) intertwined double helix. The calculations showed that gramicidin is likelyto partition into the bilayer in all of these conformations. However, the SS conformation was found to besignificantly more stable than the DS in the bilayer, in agreement with most of the experimental data. Wetested numerous transmembrane and surface orientations of gramicidin in bilayers of various widths. Ourcalculations indicate that the most favorable orientation is transmembrane, which is indeed to be expectedfrom a channel-forming peptide. The calculations demonstrate that gramicidin insertion into the membraneis likely to involve a significant deformation of the bilayer to match the hydrophobic width of the peptide(22 Å), again in good agreement with experimental data. Interestingly, deformation of the bilayer wasinduced by all of the gramicidin conformations.
-helicesand a double-stranded (DS) intertwined double helix. The calculations showed that gramicidin is likelyto partition into the bilayer in all of these conformations. However, the SS conformation was found to besignificantly more stable than the DS in the bilayer, in agreement with most of the experimental data. Wetested numerous transmembrane and surface orientations of gramicidin in bilayers of various widths. Ourcalculations indicate that the most favorable orientation is transmembrane, which is indeed to be expectedfrom a channel-forming peptide. The calculations demonstrate that gramicidin insertion into the membraneis likely to involve a significant deformation of the bilayer to match the hydrophobic width of the peptide(22 Å), again in good agreement with experimental data. Interestingly, deformation of the bilayer wasinduced by all of the gramicidin conformations.