Abstract
Protein folding is an important and yet challenging topic in current molecular biology. In this work, the folding dynamics and mechanisms of the Trp-cage mini-protein were studied with molecular dynamics simulations, in the absence and presence of water solvents. The important intermediates during the Trp-cage folding were determined by gradually decreasing the simulation temperature. The folding transition temperature was identified to be approximately 400 K, and the folding pathway was decomposed into six steps: U ↔ I 1 ↔ I 2 ↔ I 3 ↔ I 4 ↔ F 1 ↔ F 2, where U, I and F represent the unfolded, intermediate and folded states, respectively. The finding that the two helical subunits are successively formed is consistent with the experimental observations, and the Asp9/Arg16 salt bridge forms at the final stage and does not play a significant role during folding kinetics. The presence of water solvents induces hydrophobic collapse as the whole cage comparatively closes. Within aqueous solutions, the Trp-cage folding begins to contract into the meta-stable state, and by traversing the transition state it arrives at the native-like structure, which resembles the experimental structure closely.
Acknowledgements
This work was supported by grants from the Special Fund for Basic Scientific Research of Central Colleges (No. DL09EA04-2), the Major State Basic Research Development Program (No. 2004CB719902), the National Natural Science Foundation of China (No. 20903019), the Talented Funds of Northeast Forestry University (No. 220-602042) and the Cultivated Funds of Excellent Dissertation of Doctoral Degree Northeast Forestry University (No. 140-602051).