Abnormalities in the transition betweenα-helices andβ-sheets(α-βtransition)may lead to devastating neurodegenerative diseases,such as Parkinson's syndrome and Alzheimer's disease.Ionic liquids(ILs)are pote...Abnormalities in the transition betweenα-helices andβ-sheets(α-βtransition)may lead to devastating neurodegenerative diseases,such as Parkinson's syndrome and Alzheimer's disease.Ionic liquids(ILs)are potential drugs for targeted therapies against these diseases because of their excellent bioactivity and designability of ILs.However,the mechanism through which ILs regulate the aα-βtransition remains unclear.Herein,a combination of GPU-accelerated microsecond molecular dynamics simulations,correlation analysis,and machine learning was used to probe the dynamicalα-βtransition process induced by ILs of 1-alkyl-3-methylimidazolium chloride([Cnmim]cl)and its molecular mechanism.Interestingly,the cation of[C,mim]+in ILs can spontaneously insert into the peptides as free ions(n≤10)and clusters(n≥11).Such insertion can significantly inhibit theα-β,transition and the inhibiting ability for the clusters is more significant than that of free ions,where[Ciomim]+and[Ci2mim]+can reduce the maximumβ-sheet content of the peptide by 18.5%and 44.9%,respectively.Furthermore,the correlation analysis and machine learning method were used to develop a predictive model accounting for the influencing factors on theα-βtransition,which could accurately predict the effect of ILs on theα-βtransition.Overall,these quantitative results may not only deepen the understanding of the role of ILs in theα-βtransition but also guide the development of the IL-based treatments for related diseases.展开更多
基金the National Natural Science Foundation of China(21834006,22078322,21978293,and 21978027)the Youth Innovation Promotion Association of CAS(2021046,Y2021046)State Key Laboratory of Treatments and Recycling for Organic Effluents by Adsorption in Petroleum and Chemical Industry(SDHY2114).
文摘Abnormalities in the transition betweenα-helices andβ-sheets(α-βtransition)may lead to devastating neurodegenerative diseases,such as Parkinson's syndrome and Alzheimer's disease.Ionic liquids(ILs)are potential drugs for targeted therapies against these diseases because of their excellent bioactivity and designability of ILs.However,the mechanism through which ILs regulate the aα-βtransition remains unclear.Herein,a combination of GPU-accelerated microsecond molecular dynamics simulations,correlation analysis,and machine learning was used to probe the dynamicalα-βtransition process induced by ILs of 1-alkyl-3-methylimidazolium chloride([Cnmim]cl)and its molecular mechanism.Interestingly,the cation of[C,mim]+in ILs can spontaneously insert into the peptides as free ions(n≤10)and clusters(n≥11).Such insertion can significantly inhibit theα-β,transition and the inhibiting ability for the clusters is more significant than that of free ions,where[Ciomim]+and[Ci2mim]+can reduce the maximumβ-sheet content of the peptide by 18.5%and 44.9%,respectively.Furthermore,the correlation analysis and machine learning method were used to develop a predictive model accounting for the influencing factors on theα-βtransition,which could accurately predict the effect of ILs on theα-βtransition.Overall,these quantitative results may not only deepen the understanding of the role of ILs in theα-βtransition but also guide the development of the IL-based treatments for related diseases.
