The protein folding problem: global optimization of the force fields.
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.
Scheraga
H A
HA
Baker Laboratory of Chemistry, Cornell University, Ithaca, New York 14853, USA. has5@cornell.edu
Liwo
A
A
Oldziej
S
S
Czaplewski
C
C
Pillardy
J
J
Ripoll
D R
DR
Vila
J A
JA
Kazmierkiewicz
R
R
Saunders
J A
JA
Arnautova
Y A
YA
Jagielska
A
A
Chinchio
M
M
Nanias
M
M
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
D010455:Peptides; D011506:Proteins