Folding and Stabilization of Native-Sequence-Reversed Proteins.
Though the problem of sequence-reversed protein folding is largely unexplored, one might speculate that reversed native protein sequences should be significantly more foldable than purely random heteropolymer sequences. In this article, we investigate how the reverse-sequences of native proteins might fold by examining a series of small proteins of increasing structural complexity (α-helix, β-hairpin, α-helix bundle, and α/β-protein). Employing a tandem protein structure prediction algorithmic and molecular dynamics simulation approach, we find that the ability of reverse sequences to adopt native-like folds is strongly influenced by protein size and the flexibility of the native hydrophobic core. For β-hairpins with reverse-sequences that fail to fold, we employ a simple mutational strategy for guiding stable hairpin formation that involves the insertion of amino acids into the β-turn region. This systematic look at reverse sequence duality sheds new light on the problem of protein sequence-structure mapping and may serve to inspire new protein design and protein structure prediction protocols.
Institute of Quantitative Biology, Department of Physics, Zhejiang University, Hangzhou 310027, China.|Computational Biological Center, IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, USA.
Yuanzhao
Y
Zhang
Computational Biological Center, IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, USA.
Jeffrey K
JK
Weber
Institute of Quantitative Biology, Department of Physics, Zhejiang University, Hangzhou 310027, China.|Computational Biological Center, IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, USA.|Department of Chemistry, Columbia University, New York, NY 10027, USA.
Ruhong
R
Zhou
D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D017510:Protein Folding; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
D011506:Proteins