Title: The protein folding
problem: Global optimization of force fields
Author(s): Scheraga HA, Liwo A,
Oldziej S, Czaplewski C, Pillardy J, Ripoll DR, Vila JA,
Kazmierkiewicz R, Saunders JA, Arnautova YA, Jagielska A,
Chinchio M, Nanias M
Source: FRONTIERS IN BIOSCIENCE
9: 3296-3323 Suppl. S, SEP 1 2004
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.
Author Keywords: protein
folding; empirical force fields; global optimization; folding
pathways
KeyWords Plus: MULTIPLE-MINIMA
PROBLEM; CRYSTAL-STRUCTURE PREDICTION; MONTE-CARLO METHOD;
MEMBRANE-BOUND PORTION; POTENTIAL-ENERGY FUNCTIONS; DIFFUSION
EQUATION METHOD; COILED-COIL CONFORMATION; PANCREATIC TRYPSIN-INHIBITOR;
HYDROGEN-BOND INTERACTIONS; JONES ATOMIC CLUSTERS
Addresses: Scheraga HA (reprint
author), Cornell Univ, Baker Lab Chem, Ithaca, NY 14853 USA
Cornell Univ, Baker Lab Chem, Ithaca, NY 14853 USA
Publisher: FRONTIERS IN
BIOSCIENCE INC, C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL
RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA
Subject Category: BIOCHEMISTRY &
MOLECULAR BIOLOGY; CELL BIOLOGY
IDS Number: 852NS
ISSN: 1093-9946
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