内禀无序蛋白构象与带电氨基酸残基排布关系--以精氨酸和天冬氨酸组成的随机多肽为例  

Conformation of disordered peptides modulated by distributions of charged residues:Case study of random peptides composed of arginines and aspartic acids

作　　者：康文斌 王骏[1] 王炜[1] 

机构地区：[1]南京大学物理学院,南京210093 [2]湖北医药学院数理教研室,十堰442000 [3]湖北医药学院Bio-X研究中心,十堰442000

出　　处：《物理学报》2018年第5期264-271,共8页Acta Physica Sinica

基　　金：国家重点基础研究发展计划(批准号：2013CB834100);国家自然科学基金(批准号：11334004,11174133,81421091,11774157);2017年国家级大学生创新创业训练计划(批准号：201710929002);湖北医药学院研究生启动金(批准号：2011QDZR-11)资助的课题

摘　　要：内禀无序蛋白的结构特征与其氨基酸序列有着密切的联系.其中一个核心问题是正负带电氨基酸残基的排列如何影响无序蛋白或者多肽的构象?为了回答这一问题,本研究以天冬氨酸和精氨酸两种带电残基组成的随机多肽为研究对象,利用全原子蒙特卡罗模拟和温度副本交换采样方法,研究了随机多肽的电荷排布与结构之间的定性关系.结果表明:正负带电残基在序列上混合均匀时,由于肽链内部的静电吸引和排斥相互抵消,肽链倾向于形成无规卷曲的构象;正负带电残基分离时,由于长程静电相互吸引,多肽倾向于形成类β-发卡的形状.The relationship between the sequential and structural features of intrinsically disordered peptides（IDPs） has attracted much attention during the recent decade. One essential problem relating to sequence-structure relationship is how the distribution of charged residues affects the structure of IDP. In this work, we address this problem with simulations on a series of random peptides composed of arginine and aspartic acids. With the ABSINTH implicit solvation model, the structural ensembles are generated with Markov Chain Monte Carlo method and replica-exchange sampling. The relations between various structural features（including the gyration radius, the tail distance, the distance between residues, and asphericity） and the distribution of charged residues are analyzed. Several limit cases（with parts of interactions switched off） are also calculated for comparison. The conversion from extended conformations to compact structures is observed, following the demixing of negatively and positively charged residues along the sequence. For the cases with well-mixed charges, the intra-chain electrostatic repulsions and attractions are balanced, which results in a generic Flory random coil-like conformation. Differently, for the case with well-separated charged residues, the electrostatic attraction between residues distant along the sequence induces a semi-compact hairpin-like conformation.This is consistent with the observations of Pappu group. Our results suggest that the structural dependence on charge distribution would not be sensitive to the selection of amino acid, and is determined by the patterns of charges, which demonstrates the robustness of the mechanism that the charge distribution modulates the structural features in the IDP system. Our results may broaden our understanding of the sequence-structure relation of IDP system.

关 键 词：内禀无序蛋白 构象 序列 分子模拟 

分 类 号：Q51[生物学—生物化学]