title: In vitro evolution of thermodynamically stable turns.
abstract: To determine the role of primary structure in specifying turns, random sequences (guests) were substituted for the native turn sequences in a series of proteins (hosts) of differing thermodynamic stabilities.The fraction of inserts that result in active proteins is measured as a function of the stability of the host and temperature. With a highly stable host, more than half of the inserts give functional proteins. However, a smaller fraction of sequences supports folding as the stability of the host decreases, and the temperature increases. The sequences of many of the selected inserts resemble the wild-type turn, and those that diverge match other established turn preferences. Thermodynamic measurements show that turn sequences selected under stringent conditions result in the most stable proteins. Thus, beta-turns appear to be under evolutionary pressure favouring thermodynamically stable structures.
authors.affiliation: DuPont Merck Pharmaceutical Company, Wilmington, Delaware 19880-0336, USA.
authors.forename: H X
authors.initials: HX
authors.lastname: Zhou
authors.forename: R H
authors.initials: RH
authors.lastname: Hoess
authors.forename: W F
authors.initials: WF
authors.lastname: DeGrado
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D001483:Base Sequence; D005075:Biological Evolution; D015723:Gene Library; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry; D017422:Sequence Analysis, DNA; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; C034284:IgG Fc-binding protein, Streptococcus; D011994:Recombinant Proteins