聚脯氨酸-精氨酸液液相分离的分子动力学研究  

Molecular dynamics study on liquid-liquid phase separation of poly proline-arginine

作　　者：杨小均 吴梦雪 卢静鈃 严欢 王艳伟[1] 杨光参[1] YANG Xiaojun;WU Mengxue;LU Jingxing;YAN Huan;WANG Yanwei;YANG Guangcan(School of Mathematics and Physics,Wenzhou University,Wenzhou 325035,China)

机构地区：[1]温州大学数理学院,浙江温州325053

出　　处：《齐鲁工业大学学报》2025年第1期47-53,共7页Journal of Qilu University of Technology

基　　金：国家自然科学基金(12074289、11574232);浙江省自然科学基金面上项目(Y23A040004);浙江省高等教育“十四五”教学改革项目(jg20220509);浙江省研究生教育学会科研项目(2023-016);浙江省新苗(2023R451012);国家级创新创业计划(JWXC2022070)。

摘　　要：阐明液-液相分离(LLPS)中控制蛋白质和多肽行为的复杂相互作用对于揭示生物功能和功能障碍至关重要。该研究用粗粒度分子动力学方法模拟不同序列的重复聚脯氨酸和精氨酸肽(poly PR)在不同盐浓度和温度溶液中的相分离。研究结果表明,对于长度达到50的聚PR25多肽,只有在盐浓度达到2700 mmol·L-1时才会有明显的相分离现象发生,在小于这个临界盐浓度时不发生相分离,为了揭示控制多肽相分离的分子作用,在多肽体系中引入了介电常数调节剂和疏水干扰剂,模拟结果揭示了疏水和静电相互作用都是影响PR25多肽相分离的因素。此外,还研究了温度效应和氨基酸重复序列差异对相分离的影响,可见,随着温度的升高,PR25的LLPS行为受到显著抑制,并且poly PR中不同的脯氨酸-精氨酸序列会导致不同程度的相分离现象。我们的模拟结果为进一步研究液液相分离提供了新的思路。Elucidating the complex interactions that govern protein and peptide behavior in liquid-liquid phase separation(LLPS)is crucial for understanding biological functions and dysfunctions.In this study,coarse-grained molecular dynamics simulations were employed to investigate the phase separation of poly proline-arginine peptides(poly PR)with different sequences in solutions of varying concentrations and temperatures.Our findings reveal that for poly PR25 peptides with a length of 50,significant phase separation only occurs when the salt concentration reaches 2700 mmol·L-1;below this critical concentration,no phase separation is observed.To uncover the molecular mechanisms controlling peptide phase separation,dielectric constant modifiers and hydrophobic perturbants were introduced into the peptide system.The simulation results indicate that both hydrophobic and electrostatic interactions are factors influencing the phase separation of PR25 peptides.Furthermore,the effects of temperature and variations were examined in amino acid repeat sequences on phase separation.Notably,as the temperature increases,the LLPS behavior of PR25 is significantly inhibited,and different proline-arginine sequences in poly PR result in varying degrees of phase separation.Our simulation outcomes provide novel insights for further exploring liquid-liquid phase separation.

关 键 词：poly PR 液-液相分离 疏水相互作用 静电相互作用 

分 类 号：TQ028[化学工程]