title: Physics-based protein-structure prediction using a hierarchical protocol based on the UNRES force field: assessment in two blind tests.
abstract: Recent improvements in the protein-structure prediction method developed in our laboratory, based on the thermodynamic hypothesis, are described. The conformational space is searched extensively at the united-residue level by using our physics-based UNRES energy function and the conformational space annealing method of global optimization. The lowest-energy coarse-grained structures are then converted to an all-atom representation and energy-minimized with the ECEPP/3 force field. The procedure was assessed in two recent blind tests of protein-structure prediction. During the first blind test, we predicted large fragments of alpha and alpha+beta proteins [60-70 residues with C(alpha) rms deviation (rmsd) <6 A]. However, for alpha+beta proteins, significant topological errors occurred despite low rmsd values. In the second exercise, we predicted whole structures of five proteins (two alpha and three alpha+beta, with sizes of 53-235 residues) with remarkably good accuracy. In particular, for the genomic target TM0487 (a 102-residue alpha+beta protein from Thermotoga maritima), we predicted the complete, topologically correct structure with 7.3-A C(alpha) rmsd. So far this protein is the largest alpha+beta protein predicted based solely on the amino acid sequence and a physics-based potential-energy function and search procedure. For target T0198, a phosphate transport system regulator PhoU from T. maritima (a 235-residue mainly alpha-helical protein), we predicted the topology of the whole six-helix bundle correctly within 8 A rmsd, except the 32 C-terminal residues, most of which form a beta-hairpin. These and other examples described in this work demonstrate significant progress in physics-based protein-structure prediction.
authors.affiliation: Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853-1301, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ołdziej
authors.forename: C
authors.initials: C
authors.lastname: Czaplewski
authors.forename: A
authors.initials: A
authors.lastname: Liwo
authors.forename: M
authors.initials: M
authors.lastname: Chinchio
authors.forename: M
authors.initials: M
authors.lastname: Nanias
authors.forename: J A
authors.initials: JA
authors.lastname: Vila
authors.forename: M
authors.initials: M
authors.lastname: Khalili
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: Makowski
authors.forename: H D
authors.initials: HD
authors.lastname: Schafroth
authors.forename: R
authors.initials: R
authors.lastname: Kaźmierkiewicz
authors.forename: D R
authors.initials: DR
authors.lastname: Ripoll
authors.forename: J
authors.initials: J
authors.lastname: Pillardy
authors.forename: J A
authors.initials: JA
authors.lastname: Saunders
authors.forename: Y K
authors.initials: YK
authors.lastname: Kang
authors.forename: K D
authors.initials: KD
authors.lastname: Gibson
authors.forename: H A
authors.initials: HA
authors.lastname: Scheraga
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D001703:Biophysics / Q000379:methods*; D008958:Models, Molecular; D011487:Protein Conformation; D040901:Proteomics / Q000379:methods*; D013816:Thermodynamics; D020124:Thermotoga maritima
chemical_list: D001426:Bacterial Proteins