Hierarchical energy-based approach to protein-structure prediction:
Blind-test evaluation with CASP3 targets
Lee J, Liwo A, Ripoll DR, Pillardy J, Saunders JA, Gibson KD, Scheraga HA
INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY 77 (1): 90-117 MAR 5 2000
Document type: Article |
Language: English |
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Abstract:
A hierarchical approach based exclusively on finding the global minimum of an
appropriate potential energy function, without the aid of secondary structure
prediction, multiple-sequence alignment, or threading, is proposed. The
procedure starts from an extensive search of the conformational space of a
protein, using our recently developed united-residue off-lattice UNRES force
field and the conformational space annealing (CSA) method. The structures
obtained in the search are clustered into families and ranked according to their
UNRES energy Structures within a preassigned energy cutoff are gradually
converted into an all-atom representation, followed by a limited conformational
search at the all-atom level, using the electrostatically driven Monte Carlo (EDMC)
method and the ECEPP/3 force field including hydration. The approach was tested
(in the CASP3 experiment) in blind predictions on seven targets, five of which
were globular proteins with sizes ranging from 89 to 140 amino acid residues.
Comparison of the computed lowest-energy structures, with the experimental
structures, made available after the predictions were submitted, shows that
large fragments (similar to 60 residues, representing 45-80% of the proteins) of
those five globular proteins were predicted with the root mean square deviations
(RMSDs) ranging from 4 to 7 Angstrom for the C-alpha atoms, with correct
secondary structure and topology. These results constitute an important step
toward the prediction of protein structure based solely on global optimization
of a potential energy function for a given amino acid sequence. (C) 2000 John
Wiley & Sons, Inc.
Author Keywords:
protein folding, global optimization, conformational search, potential energy
function, structure prediction
KeyWords Plus:
MULTIPLE-MINIMA PROBLEM, DRIVEN MONTE-CARLO, PANCREATIC TRYPSIN-INHIBITOR,
DIFFUSION EQUATION METHOD, RESIDUE FORCE-FIELD, HYDROGEN-BOND INTERACTIONS,
MEMBRANE-BOUND PORTION, OCCURRING AMINO-ACIDS, CONFORMATIONAL-ANALYSIS,
NONBONDED INTERACTIONS