Physics-based protein-structure prediction using a hierarchical protocol based on the UNRES force field: assessment in two blind tests.
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.
Ołdziej
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S
Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853-1301, USA.
Czaplewski
C
C
Liwo
A
A
Chinchio
M
M
Nanias
M
M
Vila
J A
JA
Khalili
M
M
Arnautova
Y A
YA
Jagielska
A
A
Makowski
M
M
Schafroth
H D
HD
Kaźmierkiewicz
R
R
Ripoll
D R
DR
Pillardy
J
J
Saunders
J A
JA
Kang
Y K
YK
Gibson
K D
KD
Scheraga
H A
HA
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
D001426:Bacterial Proteins