title: Cooperative thermal denaturation of proteins designed by binary patterning of polar and nonpolar amino acids.
abstract: We previously reported a combinatorial strategy for designing alpha-helical proteins by assigning only the binary patterning of polar or nonpolar residues [Kamtekar, S., Schiffer, J. M., Xiong, H. Y., Babik, J. M., and Hecht, M. H. (1993) Science 262, 1680-1685]. Here we describe the finding that approximately half of the proteins in the original collection display some level of cooperativity in their thermal denaturation profiles. Many are monomeric in solution, demonstrating that the observed cooperativity is not merely a consequence of oligomerization. These findings demonstrate that although the combinatorial nature of the design strategy precludes explicit design of side-chain packing, binary patterning incorporates sufficient sequence information to generate de novo proteins with cooperatively folded structures. As binary partitioning of polar and nonpolar amino acids is an intrinsic part of the genetic code, these findings may bear on the early evolution of native proteins.
authors.affiliation: Department of Chemistry, Princeton University, Princeton, New Jersey 08544-1009, USA.
authors.forename: S
authors.initials: S
authors.lastname: Roy
authors.forename: M H
authors.initials: MH
authors.lastname: Hecht
mesh_terms: D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry* / Q000378:metabolism*; D002942:Circular Dichroism; D020650:Combinatorial Chemistry Techniques; D019281:Dimerization; D008969:Molecular Sequence Data; D011485:Protein Binding; D011489:Protein Denaturation; D015202:Protein Engineering; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012996:Solutions; D055672:Static Electricity; D013696:Temperature; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D011506:Proteins; D011994:Recombinant Proteins; D012996:Solutions