title: A method for predicting protein structure from sequence.
abstract: BACKGROUND
  The ability to predict the native conformation of a globular protein from its amino-acid sequence is an important unsolved problem of molecular biology. We have previously reported a method in which reduced representations of proteins are folded on a lattice by Monte Carlo simulation, using statistically-derived potentials. When applied to sequences designed to fold into four-helix bundles, this method generated predicted conformations closely resembling the real ones.
  
  
  RESULTS
  We now report a hierarchical approach to protein-structure prediction, in which two cycles of the above-mentioned lattice method (the second on a finer lattice) are followed by a full-atom molecular dynamics simulation. The end product of the simulations is thus a full-atom representation of the predicted structure. The application of this procedure to the 60 residue, B domain of staphylococcal protein A predicts a three-helix bundle with a backbone root mean square (rms) deviation of 2.25-3 A from the experimentally determined structure. Further application to a designed, 120 residue monomeric protein, mROP, based on the dimeric ROP protein of Escherichia coli, predicts a left turning, four-helix bundle native state. Although the ultimate assessment of the quality of this prediction awaits the experimental determination of the mROP structure, a comparison of this structure with the set of equivalent residues in the ROP dime- crystal structure indicates that they have a rms deviation of approximately 3.6-4.2 A.
  
  
  CONCLUSIONS
  Thus, for a set of helical proteins that have simple native topologies, the native folds of the proteins can be predicted with reasonable accuracy from their sequences alone. Our approach suggest a direction for future work addressing the protein-folding problem.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, 10666 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: J
authors.initials: J
authors.lastname: Skolnick
authors.forename: A
authors.initials: A
authors.lastname: Kolinski
authors.forename: C L
authors.initials: CL
authors.lastname: Brooks
authors.forename: A
authors.initials: A
authors.lastname: Godzik
authors.forename: A
authors.initials: A
authors.lastname: Rey