The chemistry of ion transport at the molecular level is understood only in quite general terms.
The aim of this research is to enhance the understanding of rapid and selective ion transport through transmembrane channels at the molecular level. The gramicidin family of channels is a powerful system for investigating the interactions among ion, protein and lipid during the transport process. The gramicidin family represents a related series of peptides of known structure, in which specific changes in structure and the specific placement of polarizable substituents can be correlated with channel selectivity, stability, lipid dependence and transport properties. Advantages of the gramicidin family include: ideal selectivity for monovalent cations, partial intercationic specificity, single-file characteristics, its generally accepted structure, the availability of natural and synthetic analogues, and a sensitive assay for the equivalence of native and analogue conformations. This research will address the chemical control of the elementary steps of transport using both kinetic and equilibrium techniques. Site- specific modifications of the gramicidin channel will be used to (i) investigate channel properties and structure-function relationships, and (ii) design new molecular features that extend the function of the parent molecule. The results are expected to reveal general principles that govern ion transport through biological transmembrane channels, a process that is important for intercellular communication and for signal transmission in the nervous system.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Biophysical Chemistry Study Section (BBCB)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Arkansas at Fayetteville
Schools of Arts and Sciences
United States
Zip Code
Siegel, D P; Cherezov, V; Greathouse, D V et al. (2006) Transmembrane peptides stabilize inverted cubic phases in a biphasic length-dependent manner: implications for protein-induced membrane fusion. Biophys J 90:200-11
Lundbaek, Jens A; Birn, Pia; Hansen, Anker J et al. (2004) Regulation of sodium channel function by bilayer elasticity: the importance of hydrophobic coupling. Effects of Micelle-forming amphiphiles and cholesterol. J Gen Physiol 123:599-621
Goforth, Robyn L; Chi, Aung K; Greathouse, Denise V et al. (2003) Hydrophobic coupling of lipid bilayer energetics to channel function. J Gen Physiol 121:477-93
de Planque, Maurits R R; Bonev, Boyan B; Demmers, Jeroen A A et al. (2003) Interfacial anchor properties of tryptophan residues in transmembrane peptides can dominate over hydrophobic matching effects in peptide-lipid interactions. Biochemistry 42:5341-8
Hwang, Tzyh-Chang; Koeppe 2nd, Roger E; Andersen, Olaf S (2003) Genistein can modulate channel function by a phosphorylation-independent mechanism: importance of hydrophobic mismatch and bilayer mechanics. Biochemistry 42:13646-58
de Planque, Maurits R R; Boots, Jan-Willem P; Rijkers, Dirk T S et al. (2002) The effects of hydrophobic mismatch between phosphatidylcholine bilayers and transmembrane alpha-helical peptides depend on the nature of interfacially exposed aromatic and charged residues. Biochemistry 41:8396-404
Strandberg, Erik; Morein, Sven; Rijkers, Dirk T S et al. (2002) Lipid dependence of membrane anchoring properties and snorkeling behavior of aromatic and charged residues in transmembrane peptides. Biochemistry 41:7190-8
van der Wel, Patrick C A; Strandberg, Erik; Killian, J Antoinette et al. (2002) Geometry and intrinsic tilt of a tryptophan-anchored transmembrane alpha-helix determined by (2)H NMR. Biophys J 83:1479-88
Demmers, J A; van Duijn, E; Haverkamp, J et al. (2001) Interfacial positioning and stability of transmembrane peptides in lipid bilayers studied by combining hydrogen/deuterium exchange and mass spectrometry. J Biol Chem 276:34501-8
Greathouse, D V; Goforth, R L; Crawford, T et al. (2001) Optimized aminolysis conditions for cleavage of N-protected hydrophobic peptides from solid-phase resins. J Pept Res 57:519-27

Showing the most recent 10 out of 58 publications