Acta Phys. -Chim. Sin. ›› 2013, Vol. 29 ›› Issue (09): 1842-1850.doi: 10.3866/PKU.WHXB201307011

• REVIEW • Previous Articles     Next Articles

Research Progress of the Trp-Cage Formation and Its Folding Mechanism

WU Xiao-Min1,2, YUAN Xiao-Hui3, XUE Shu-Lei1, ZHA Ling-Sheng1, WANG Guang-Li1, ZHANG Hai-Jun1   

  1. 1 Key Laboratory of Resource and Plant Biology of Anhui Province, College of Life Science, Huaibei Normal University, Huaibei 235000, Anhui Province, P. R. China;
    2 National Local Joint Engineering Laboratory of Bio-resource Ecological Utilization, Northeast Forestry University, Harbin 150040, P. R. China;
    3 Institute of Biomedicine, Jinan University, Guangzhou 510632, P. R. China
  • Received:2013-02-26 Revised:2013-06-28 Published:2013-08-28
  • Contact: WU Xiao-Min, ZHANG Hai-Jun;
  • Supported by:

    The project was supported by the National Natural Science Foundation of China (81272377, 31100083), Natural Science Foundation of Anhui Province, China (1208085QC58), Natural Science Foundation fromEducational Commission of Anhui Province, China (KJ2012B163, 2012SQRL225), and Talented Funds of Huaibei Normal University, China (600698).


Protein folding is considered one of the most important topics in structural biology. An in-depth understanding of the folding-function relationship is one of the most important subjects for biologists, and is of interest to scientific researchers in other disciplines. The folding of proteins is often completed within the order of milliseconds to seconds, whereas the underlying atomistic details corresponding to structural alterations and intermolecular interactions often occur on the nanosecond or even smaller timescales. Accordingly, the unambiguous description of complicated folding behaviors remains inaccessible to routine experimental and theoretically-calculated resolutions. In this paper, we reviewthe problems that exist in recent experimental and theoretical studies examining the protein folding mechanism. The Trp-cage is a fast-folding mini-protein containing merely 20 amino acid residues, but adopts a well-packed hydrophobic core and tertiary contacts. Herein, we use the Trp-cage as an example and summarize the experimental and theoretical research carried out on the Trp-cage formation and its folding mechanism. The presentation primarily focuses on three aspects: (1) the folding temperature; (2) the folding initiation and proposed folding mechanisms; and (3) the role of key residues and its driving force for the folding of the Trp-cage mini-protein. Finally, we provide some suggestions on how to effectively simplify the complicated interaction networks of the Trp-cage mini-protein and decrease the complexity of the folding mechanism. This helps us to clarify the respective and cooperative contributions of residues involved in the formation of the Trp-cage and its folding dynamics, as well as provide useful insights for folding studies and more efficient rational peptide design.

Key words: Experimental and theoretical simulation, Folding mechanism, Transition temperature, Residue mutation, Key residue


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