Folding nucleus and unfolding dynamics of protein 2GB1
Xuefeng Wei(韦学锋)1,2 and Yanting Wang(王延颋)1,2,†
1 CAS Key Laboratory of Theoretical Physics, Institute of Theoretical Physics, Chinese Academy of Sciences, Beijing 100190, China; 2 School of Physical Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
Abstract The folding of many small proteins is kinetically a two-state process with one major free-energy barrier to overcome, which can be roughly regarded as the inverse process of unfolding. In this work, we first use a Gaussian network model to predict the folding nucleus corresponding to the major free-energy barrier of protein 2GB1, and find that the folding nucleus is located in the β -sheet domain. High-temperature molecular dynamics simulations are then used to investigate the unfolding process of 2GB1. We draw free-energy surface from unfolding simulations, taking RMSD and contact number as reaction coordinates, which confirms that the folding of 2GB1 is kinetically a two-state process. The comparison of the contact maps before and after the free energy barrier indicates that the transition from native to non-native structure of the protein is kinetically caused by the destruction of the β -sheet domain, which manifests that the folding nucleus is indeed located in the β -sheet domain. Moreover, the constrained MD simulation further confirms that the destruction of the secondary structures does not alter the topology of the protein retained by the folding nucleus. These results provide vital information for upcoming researchers to further understand protein folding in similar systems.
Fund: Project supported by the Strategic Priority Research Program of Chinese Academy of Sciences (Grant No. XDA17010504) and the National Natural Science Foundation of China (Grant No. 11947302).
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