title: LINUS: a hierarchic procedure to predict the fold of a protein.
abstract: We describe LINUS, a hierarchic procedure to predict the fold of a protein from its amino acid sequence alone. The algorithm, which has been implemented in a computer program, was applied to large, overlapping fragments from a diverse test set of 7 X-ray-elucidated proteins, with encouraging results. For all proteins but one, the overall fragment topology is well predicted, including both secondary and supersecondary structure. The algorithm was also applied to a molecule of unknown conformation, groES, in which X-ray structure determination is presently ongoing. LINUS is an acronym for Local Independently Nucleated Units of Structure. The procedure ascends the folding hierarchy in discrete stages, with concomitant accretion of structure at each step. The chain is represented by simplified geometry and folds under the influence of a primitive energy function. The only accurately described energetic quantity in this work is hard sphere repulsion--the principal force involved in organizing protein conformation [Richards, F. M. Ann. Rev. Biophys. Bioeng. 6:151-176, 1977]. Among other applications, the method is a natural tool for use in the human genome initiative.
authors.affiliation: Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: R
authors.initials: R
authors.lastname: Srinivasan
authors.forename: G D
authors.initials: GD
authors.lastname: Rose
mesh_terms: D000465:Algorithms; D000596:Amino Acids / Q000737:chemistry; D001059:Apoproteins / Q000737:chemistry; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry; D018835:Chaperonin 10 / Q000737:chemistry; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D003573:Cytochrome b Group / Q000737:chemistry; D029968:Escherichia coli Proteins; D050556:Fatty Acid-Binding Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D018996:Myelin P2 Protein / Q000737:chemistry; D009211:Myoglobin / Q000737:chemistry; D009363:Neoplasm Proteins; D010970:Plastocyanin / Q000737:chemistry; D017510:Protein Folding; D017433:Protein Structure, Secondary; D015843:Serpins / Q000737:chemistry; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D001059:Apoproteins; D002352:Carrier Proteins; D018835:Chaperonin 10; D003573:Cytochrome b Group; D029968:Escherichia coli Proteins; D050556:Fatty Acid-Binding Proteins; D018996:Myelin P2 Protein; D009211:Myoglobin; D009363:Neoplasm Proteins; D015843:Serpins; C010857:apomyoglobin; D010970:Plastocyanin; C017850:cytochrome b562, E coli; D013762:Tetrahydrofolate Dehydrogenase