The protein folding problem: Global optimization of force fields

被引：26

作者：

Scheraga, HA ^{[1
]}

Liwo, A ^{[1
]}

Oldziej, S ^{[1
]}

Czaplewski, C ^{[1
]}

Pillardy, J ^{[1
]}

Ripoll, DR ^{[1
]}

Vila, JA ^{[1
]}

Kazmierkiewicz, R ^{[1
]}

Saunders, JA ^{[1
]}

Arnautova, YA ^{[1
]}

Jagielska, A ^{[1
]}

Chinchio, M ^{[1
]}

Nanias, M ^{[1
]}

机构：

[1] Cornell Univ, Baker Lab Chem, Ithaca, NY 14853 USA

来源：

FRONTIERS IN BIOSCIENCE-LANDMARK | 2004年 / 9卷

关键词：

protein folding; empirical force fields; global optimization; folding pathways;

D O I：

10.2741/1482

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：3296 / 3323

页数：28

共 138 条

[1] PRINCIPLES THAT GOVERN FOLDING OF PROTEIN CHAINS [J].