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BioMed Research International
Volume 2013, Article ID 973867, 9 pages
Research Article

Dynamic Folding Pathway Models of the Trp-Cage Protein

1Korea Research Institute of Standards and Science, Daejon 305-600, Republic of Korea
2School of Liberal Arts and Sciences, Korea National University of Transportation, Chungju 380-702, Republic of Korea
3Department of Physics and Astronomy, University of South Carolina, Columbia, SC 29208, USA

Received 5 April 2013; Accepted 10 June 2013

Academic Editor: Themis Lazaridis

Copyright © 2013 In-Ho Lee and Seung-Yeon Kim. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Using action-derived molecular dynamics (ADMD), we study the dynamic folding pathway models of the Trp-cage protein by providing its sequential conformational changes from its initial disordered structure to the final native structure at atomic details. We find that the numbers of native contacts and native hydrogen bonds are highly correlated, implying that the native structure of Trp-cage is achieved through the concurrent formations of native contacts and native hydrogen bonds. In early stage, an unfolded state appears with partially formed native contacts (~40%) and native hydrogen bonds (~30%). Afterward, the folding is initiated by the contact of the side chain of Tyr3 with that of Trp6, together with the formation of the N-terminal α-helix. Then, the C-terminal polyproline structure docks onto the Trp6 and Tyr3 rings, resulting in the formations of the hydrophobic core of Trp-cage and its near-native state. Finally, the slow adjustment processes of the near-native states into the native structure are dominant in later stage. The ADMD results are in agreement with those of the experimental folding studies on Trp-cage and consistent with most of other computational studies.