title: The protein folding problem: global optimization of the force fields.
abstract: The evolutionary development of a theoretical approach to the protein folding problem, in our laboratory, is traced. The theoretical foundations and the development of a suitable empirical all-atom potential energy function and a global optimization search are examined. Whereas the all-atom approach has thus far succeeded for relatively small molecules and for alpha-helical proteins containing up to 46 residues, it has been necessary to develop a hierarchical approach to treat larger proteins. In the hierarchical approach to single- and multiple-chain proteins, global optimization is carried out for a simplified united residue (UNRES) description of a polypeptide chain to locate the region in which the global minimum lies. Conversion of the UNRES structures in this region to all-atom structures is followed by a local search in this region. The performance of this approach in successive CASP blind tests for predicting protein structure by an ab initio physics-based method is described. Finally, a recent attempt to compute a folding pathway is discussed.
authors.affiliation: Baker Laboratory of Chemistry, Cornell University, Ithaca, New York 14853, USA. has5@cornell.edu
authors.forename: H A
authors.initials: HA
authors.lastname: Scheraga
authors.forename: A
authors.initials: A
authors.lastname: Liwo
authors.forename: S
authors.initials: S
authors.lastname: Oldziej
authors.forename: C
authors.initials: C
authors.lastname: Czaplewski
authors.forename: J
authors.initials: J
authors.lastname: Pillardy
authors.forename: D R
authors.initials: DR
authors.lastname: Ripoll
authors.forename: J A
authors.initials: JA
authors.lastname: Vila
authors.forename: R
authors.initials: R
authors.lastname: Kazmierkiewicz
authors.forename: J A
authors.initials: JA
authors.lastname: Saunders
authors.forename: Y A
authors.initials: YA
authors.lastname: Arnautova
authors.forename: A
authors.initials: A
authors.lastname: Jagielska
authors.forename: M
authors.initials: M
authors.lastname: Chinchio
authors.forename: M
authors.initials: M
authors.lastname: Nanias
mesh_terms: D000465:Algorithms; D001703:Biophysics / Q000379:methods; D019295:Computational Biology / Q000379:methods; D003460:Crystallization; D004058:Diffusion; D015233:Models, Statistical; D009010:Monte Carlo Method; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D012984:Software; D055672:Static Electricity
chemical_list: D010455:Peptides; D011506:Proteins