The protein folding problem: global optimization of the force fields.

H A Scheraga; A Liwo; S Oldziej; C Czaplewski; J Pillardy; D R Ripoll; J A Vila; R Kazmierkiewicz; J A Saunders; Y A Arnautova; A Jagielska; M Chinchio; M Nanias

doi:10.2741/1482

PubMed · 15353359

The protein folding problem: global optimization of the force fields.

H A Scheraga·A Liwo·S Oldziej·C Czaplewski·J Pillardy·D R Ripoll·J A Vila·R Kazmierkiewicz·J A Saunders·Y A Arnautova·A Jagielska·M Chinchio·M Nanias

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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.

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Algorithms Biophysics Computational Biology Crystallization Diffusion Models, Statistical Monte Carlo Method Peptides Protein Conformation Protein Folding Protein Structure, Secondary Proteins Software Static Electricity Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.

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H A Scheraga, A Liwo, S Oldziej, C Czaplewski, J Pillardy, D R Ripoll, J A Vila, R Kazmierkiewicz, J A Saunders, Y A Arnautova, A Jagielska, M Chinchio, M Nanias. 2004-09-01. The protein folding problem: global optimization of the force fields.. https://doi.org/10.2741/1482

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