聚酰胺-胺树枝形大分子导致α-突触核蛋白聚集动力学变缓  

The Aggregation Dynamics ofα-Synucleins Slowed Down by Polyamindoamine

作　　者：秦超然 黄瑞静 宋祥燕 田文得[1] Chao-ran Qin;Rui-jing Huang;Xiang-yan Song;Wen-de Tian(Center for Soft Condensed Matter Physics&Interdisciplinary Research,School of Physical Science and Technology,Soochow University,Suzhou 215006)

机构地区：[1]苏州大学软凝聚态物理及交叉研究中心物理科学与技术学院,苏州215000

出　　处：《高分子学报》2023年第1期87-94,共8页Acta Polymerica Sinica

基　　金：国家自然科学基金(基金号21474074)资助项目.

摘　　要：采用基于Martini力场的粗粒化分子动力学模拟研究了聚酰胺-胺(PAMAM)树枝形大分子对α-突触核蛋白NAC区域聚集行为的影响,发现PAMAM树枝形分子的存在延缓了NAC区域聚集过程,增长了聚集体形成的时间.团簇形成的主要时间段里,大小与时间满足一定标度关系(~tγ),且存在PAMAM时,标度指数γ减小.PAMAM大分子的代数和浓度越高,聚集体形成时间就越长;研究结果支持实验提出的“动力学抑制”猜想.Inhibition of fibril assembly is a potential therapeutic strategy in neurodegenerative disorders such as Parkinson’s and Alzheimer’s diseases.The NAC,a fragment ofα-synuclein,is considered to be the key region ofα-synuclein that causes Parkinson’s disease.It has been recently shown that the polyamidoamine(PAMAM)dendrimer is promising candidate for the treatment of Parkinson’s diseases.However,it is still not very clear that how and why the PAMAM could inhibit the protein aggegration.In this study,the interaction between PAMAM dendrimers and NAC fragments was investigated by molecular dynamics simulation.The coarse-grained Martini field was adopted for PAMAM and proteins and the effects of generation and concentration of PAMAM dendrimers on the aggregation dynamics were studied.We mainly built nine systems and G3-G5 PAMAM dendrimers were used.The systems forα-synucleins of 10.4 mmol/L were built without PAMAM,and with 0.80 and 1.04 mmol/L PAMAM dendrimers,respectively.All systems are simulated with a long time of 5000 ns.In the Martini force field,the real time is about 20μs.It was found that the addition of PAMAM molecules could slow down the aggregation process and increase the formation time of the largest cluster.The larger the dendrimer generation and the higher concentration,the larger the degree of inhibition of the NAC aggregation.Taking the existence of 5 clusters in the box as the criterion,the aggregation time is about 180 ns for the system without PAMAM dendrimers,~230 ns for the system with five G3-PAMAM dendrimers,~400 ns for the system with five G4-PAMAM dendrimers,~400 ns for the system with three G5-PAMAM dendrimers,and~500 ns for the system with five G5-PAMAM dendrimers.Meanwhile,there exists a scaling relation between cluster size,S,and simulation time,t,with S~tγ.When adding PAMAM,γ=0.54,which is smaller than that without PAMAM,γ=0.69.In addition,in our parameter spaces,the disaggeration of the existing NAC cluster was observed when dendrimers were added in the system.Our results

关 键 词：分子动力学模拟 聚酰胺-胺树枝形分子 蛋白质聚集 

分 类 号：TQ317[化学工程—高聚物工业] R742.5[医药卫生—神经病学与精神病学]