title: A heuristic approach to predicting the tertiary structure of bovine somatotropin.
abstract: A combination of a heuristic approach and energy minimization was used to predict the three-dimensional structure of bovine somatotropin (bSt), also known as bovine growth hormone, a protein of 191 amino acids. The starting points for energy minimizations were generated from the following two types of inputs: (a) the amino acid sequence and (b) the heuristic inputs, which were derived according to physical, chemical, and biological principles by piecing together all useful information available. The predicted 3-D structure of the bSt molecule has all the features observed in four-helix bundle proteins. The four alpha-helices in bSt are intimately packed to form an assembly with an approximately square cross section. All the adjacent alpha-helices are antiparallel, with a somewhat tilted angle between each of the adjacent pairs so that the assembly of the four helices looks like a left-handed twisted bundle. There are two disulfide bonds in the bSt structure: one "hooking" the middle of a long loop with helix 4 so as to pull the long loop onto the surface of the helix bundle and the other "hooking" the C-terminal segment with the same helix so as to force the C-terminal segment to bend toward the helix bundle. As a consequence, a considerable part of the surface of the four-helix bundle is closely packed or intimately embraced by the loop segments. The predicted bSt structure has a hydrophobic core and a hydrophilic exterior surface. The energetic analysis of the predicted bSt structure indicates that the interaction between helices and loops plays a dominant role in stabilizing the four-helix bundle structure from the viewpoint of both electrostatic and nonbonded interactions. A technique called FOLD was meanwhile developed, by which one can fold a polypeptide chain into any shape as desired. This tool proved to be very useful during the heuristic model-building process.
authors.affiliation: Computational Chemistry, Upjohn Laboratories, Kalamazoo, Michigan 49001.
authors.forename: L
authors.initials: L
authors.lastname: Carlacci
authors.forename: K C
authors.initials: KC
authors.lastname: Chou
authors.forename: G M
authors.initials: GM
authors.lastname: Maggiora
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D013006:Growth Hormone / Q000031:analogs & derivatives* / Q000737:chemistry; D006728:Hormones / Q000737:chemistry; D019382:Human Growth Hormone; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012689:Sequence Homology, Nucleic Acid; D013237:Stereoisomerism; D013816:Thermodynamics; D014961:X-Ray Diffraction
chemical_list: D006728:Hormones; D019382:Human Growth Hormone; D013006:Growth Hormone