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Updated: Jul 23, 2025

A Protocol for Computer-Based Protein Structure and Function Prediction
Published on: November 3, 2011
The "Beacon" Structural Model of Protein Folding: Application for Trp-Cage in Water
Qiang Sun1, Xian He1, Yanfang Fu1
1Key Laboratory of Orogenic Belts and Crustal Evolution, Ministry of Education, The School of Earth and Space Sciences, Peking University, Beijing 100871, China.
Abstract:
Protein folding is a process in which a polypeptide must undergo folding process to obtain its three-dimensional structure. Thermodynamically, it is a process of enthalpy to overcome the loss of conformational entropy in folding. Folding is primarily related to hydrophobic interactions and intramolecular hydrogen bondings. During folding, hydrophobic interactions are regarded to be the driving forces, especially in the initial structural collapse of a protein. Additionally, folding is guided by the strong interactions within proteins, such as intramolecular hydrogen bondings related to the α-helices and β-sheets of proteins. Therefore, a protein is divided into the folding key (FK) regions related to intramolecular hydrogen bondings and the non-folding key (non-FK) regions. Various conformations are expected for FK and non-FK regions. Different from non-FK regions, it is necessary for FK regions to form the specific conformations in folding, which are regarded as the necessary folding pathways (or "beacons"). Additionally, sequential folding is expected for the FK regions, and the intermediate state is found during folding. They are reflected on the local basins in the free energy landscape (FEL) of folding. To demonstrate the structural model, molecular dynamics (MD) simulations are conducted on the folding pathway of the TRP-cage in water.
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