The Folding Behaviors Of Macromolecular In Bulk And Confinement

A lot of small,single-domain proteins can fold to their native structures spontaneously.However,the folding of some proteins needs to be aided by chaperones.It's not very clear that how chaperones assist protein folding.To the best of our knowledge,the folding pathways and native structure of protein are determined by the sequence,whereas how to fold for single semiflexible homopolymers and what are the differences in folding behavior between semiflexible homopolymers and proteins remain to be elucidated.In this article,we studied:(1)the effects of chaperones on the folding of frustrated proteins;(2)the thermodynamics and kinetics of the folding of single semiflexible homopolymers.(1)We employed db models and db+MJh? model to comparatively study the folding behaviors of three small proteins Im7,Im9,and A39V/N53P/V55 L Fyn SH3 domain confined into cages with various sizes.As a decrease of the repulsive cavity size,nonnative interactions for the three proteins increase,especially in the unfolded state,leading to a stabilization of the unfolded state.The increase in stability and folding rate based on the db+MJh? model are much smaller than that by the db model.In particular,the folding rate of Im7 decreases with reducing the cavity size under zero-denaturant condition.The population of the intermediate increases with decreasing the cavity size.In attractive confinement,the folding stability in attractive cavity relative to that in purely repulsive confinement essentially decreases with increasing the strength of attractive interaction.The curve of folding rates is also related to attractive strength.This study should be useful to understand the effect of chaperone on the folding of frustrated proteins with nonnative interactions.(2)We systematically studied the thermodynamic and kinetic behaviors of semiflexible homopolymers by Langevin dynamics simulations.In line with experiments,a rich variety of folding products are observed in our more complete diagram of states.The population of the intermediate occurring in the folding process increases as the temperature decreases,which leads to a severe chevron rollover for the folding arm.The folding paths for the semiflexible homopolymer,from the coil state to the toroidal state,are diverse and the distribution of folding pathways could be tuned by solvent quality.Moreover,in the processes of knotting,three types of mechanisms are discovered,namely plugging,lipknotting,and sliding.This study should be helpful to getting insight into the general principles of protein folding.