Abstract
We review the studies on the folding mechanism of the β-hairpin tryptophan zipper 2 (trpzip2) and present some additional computational results to refine the picture of folding heterogeneity and pathways. We show that trpzip2 can have a two-state or a multi-state folding pattern, depending on whether it folds within the native basin or through local state basins on the high-dimensional free energy surface; Trpzip2 can fold along different pathways according to the packing order of tryptophan pairs. We also point out some important problems related to the folding mechanism of trpzip2 that still need clarification, e.g., a wide distribution of the computed conformations for the transition state ensemble.
Highlights
The β-hairpin is one of the smallest protein building blocks that has several qualities ascribed to proteins
The folding heterogeneity of trpzip2 may be caused by both multiple independent pathways and different probabilities staying in the non-native basins
These results indicate that all the folding pathways, whenever zip-out, zip-in or middle-out, are related to the correct formations of the native hydrophobic core or partial native hydrophobic cores. This is in agreement with the generally accepted view that the main driving force of protein folding is the hydrophobic one. From these studies of the trpzip2, we can conclude the following: (1) The free energy landscape of the trpzip2 folding and unfolding is very rough at normal temperatures due to the multiple tryptophan interactions
Summary
The β-hairpin is one of the smallest protein building blocks that has several qualities ascribed to proteins. Understanding the folding mechanisms of different β-hairpins can provide important insights into the protein folding problem, their folding thermodynamics and kinetics have been investigated extensively by experiments and theoretical simulations. Sci. 2009, 10 key aims has been to understand the mechanism of β-hairpin folding These studies have provided many insights into their behaviors and led to different proposed folding mechanisms. The zipper model assumes that the folding of GB1 starts from the turn and propagates toward the tails by forming hydrogen bonds sequentially and the hydrophobic cluster forms later This folding mechanism is supported by subsequent experiments and some simulations [5,6]. The folding kinetics and thermodynamics of the trpzip have been extensively investigated both experimentally and computationally [6,14,15,16,17,18,19,20,21,22,23,24]
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