title: Modeling protein structures: construction and their applications.
abstract: Although no general solution to the protein folding problem exists, the three-dimensional structures of proteins are being successfully predicted when experimentally derived constraints are used in conjunction with heuristic methods. In the case of interleukin-4, mutagenesis data and CD spectroscopy were instrumental in the accurate assignment of secondary structure. In addition, the tertiary structure was highly constrained by six cysteines separated by many residues that formed three disulfide bridges. Although the correct structure was a member of a short list of plausible structures, the "best" structure was the topological enantiomer of the experimentally determined conformation. For many proteases, other experimentally derived structures can be used as templates to identify the secondary structure elements. In a procedure called modeling by homology, the structure of a known protein is used as a scaffold to predict the structure of another related protein. This method has been used to model a serine and a cysteine protease that are important in the schistosome and malarial life cycles, respectively. The model structures were then used to identify putative small molecule enzyme inhibitors computationally. Experiments confirm that some of these nonpeptidic compounds are active at concentrations of less than 10 microM.
authors.affiliation: Department of Pharmaceutical Chemistry, University of California, San Francisco 94143-0446.
authors.forename: C S
authors.initials: CS
authors.lastname: Ring
authors.forename: F E
authors.initials: FE
authors.lastname: Cohen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D015847:Interleukin-4 / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins; D015847:Interleukin-4