Ionic liquids inhibit the dynamic transition fromα-helices toβ-sheets in peptides  

作　　者：Ju Liu Yanlei Wang Feng Huo Hongyan He 

机构地区：[1]Beijing Key Laboratory of Ionic Liquids Clean Process,State Key Laboratory of Mesoscience and Engineering,CAS Key Laboratory of Green Process and Engineering,Instituteof Process Engineering,ChineseAcademyof Sciences,Beijing100190,China [2]Longzihu New Energy Laboratory,Zhengzhou Institute of Emerging Industrial Technology,Henan University,Zhengzhou 450000,China [3]University of Chinese Academyof Sciences,Beijing100049,China

出　　处：《Fundamental Research》2024年第4期777-784,共8页自然科学基础研究（英文版）

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).

摘　　要：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([C_(n)mim]cl)and its molecular mechanism.Interestingly,the cation of [C_(n)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[C_(12)mim]+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.

关 键 词：α-βtransition Moleculardynamics simulation lonic liquids Machine learning Membrane channel protein 

分 类 号：O62[理学—有机化学]