title: De novo design, synthesis and characterization of membrane-active peptides.
abstract: Our current level of understanding of membrane-protein folding is primitive, but it is beginning to advance. Previously [Choma, Gratkowski, Lear and DeGrado (2000) Nat. Struct. Biol. 7, 161-166], we described studies of the association in detergent micelles of short, simple-sequence hydrophobic peptides modified from the sequence of the water-soluble, homodimeric coiled-coil GCN4-P1 peptide using the principle that the interiors of membrane proteins are similar to those of water-soluble proteins. Here, we discuss more quantitative aspects of the association equilibrium and compare the free energies of association of a number of mutant peptides designed to explore specific features responsible for the association.
authors.affiliation: The Johnson Research Foundation, Department of Biochemistry & Biophysics, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6059, USA. lear@mail.med.upenn.edu
authors.forename: J D
authors.initials: JD
authors.lastname: Lear
authors.forename: H
authors.initials: H
authors.lastname: Gratkowski
authors.forename: W F
authors.initials: WF
authors.lastname: DeGrado
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000737:chemistry; D019281:Dimerization; D015195:Drug Design; D005656:Fungal Proteins / Q000096:biosynthesis* / Q000138:chemical synthesis / Q000737:chemistry; D007700:Kinetics; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000138:chemical synthesis / Q000737:chemistry; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D017510:Protein Folding; D011494:Protein Kinases / Q000096:biosynthesis* / Q000138:chemical synthesis / Q000737:chemistry; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D029701:Saccharomyces cerevisiae Proteins
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D008565:Membrane Proteins; D010455:Peptides; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases