title: Noncontact dipole effects on channel permeation. II. Trp conformations and dipole potentials in gramicidin A.
abstract: The four Trp dipoles in the gramicidin A (gA) channel modulate channel conductance, and their side chain conformations should therefore be important, but the energies of different conformations are unknown. A conformational search for the right-handed helix based on molecular mechanics in vacuo yielded 46 conformations within 20 kcal/mol of the lowest energy conformation. The two lowest energy conformations correspond to the solid-state and solution-state NMR conformations, suggesting that interactions within the peptide determine the conformation. For representative conformations, the electrostatic potential of the Trp side chains on the channel axis was computed. A novel application of the image-series method of. Biophys. J. 9:1160-1170) was introduced to simulate the polarization of bulk water by the Trp side chains. For the experimentally observed structures, the CHARm toph19 potential energy (PE) of a cation in the channel center is -1.65 kcal/mol without images. With images, the PE is -1.9 kcal/mol, demonstrating that the images further enhance the direct dipole effect. Nonstandard conformations yielded less favorable PEs by 0.4-1.1 kcal/mol.
authors: Department of Chemistry, Colby College, Waterville, Maine 04901, USA.
authors: A E
authors: AE
authors: Dorigo
authors: D G
authors: DG
authors: Anderson
authors: D D
authors: DD
authors: Busath
mesh_terms: D000595:Amino Acid Sequence; D055592:Biophysical Phenomena; D001703:Biophysics; D004553:Electric Conductivity; D006096:Gramicidin / Q000737:chemistry*; D007473:Ion Channels / Q000737:chemistry*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D055672:Static Electricity; D013816:Thermodynamics; D014364:Tryptophan / Q000737:chemistry
chemical_list: D007473:Ion Channels; D006096:Gramicidin; D014364:Tryptophan