从静电吸引到疏水锚定:Lys-Ala多肽链与POPS/POPC膜相互作用的比较分析OACHSSCD

Aims:This paper aims to investigate the regulatory mechanism of physicochemical properties of lipid membranes on protein structure and adsorption behavior.Methods:Polypeptide chains composed of hydrophilic lysine(Lys)and hydrophobic alanine(Ala)with varied charged ratios and spatial distributions were selected and respectively combined with POPS/POPC membranes to construct composite systems for comparative investigation.The coarse-grained polypeptide chains with various positive charge ratios and consecutive charged residue numbers were constructed by VMD software.Molecular dynamics simulations were performed to analyze the conformational evolution and adsorption characteristics of the polypeptide chains under the influence of lipid membranes.Results:The POPS membrane induced a two-dimensional spread conformation of polypeptide chains by electrostatic adsorption,leading to a larger radius of gyration than in the neutral POPC bilayers.In both membrane environments,the root-mean-square fluctuations of the polypeptide chains exhibited a symmetric double-well distribution,with high values at both ends and low values in the middle.Moreover,the fluctuation amplitude of lysine(Lys)residues was higher than that of alanine(Ala).It reflected the influence of terminal dynamics and charged residues on chain flexibility.The adsorption behavior of polypeptides on the lipid membranes differed markedly.On the anionic POPS,polypeptide chains containing Lys were stably adsorbed via electrostatic interactions,whereas the all-Ala chain was repelled due to lacking electrostatic attraction and experiencing hydrophilic repulsion.On the zwitterionic POPC,only the all-Ala polypeptide chain adsorbed via hydrophobic interactions,while chains containing Lys residues failed to adsorb.Conclusions:Lipid membranes regulate the structural stability and dynamic conformational transitions of polypeptide chains through electrostatic and hydrophobic interactions.These studies on the adsorption processes of proteins onto different lipid membranes provide a theoretical foundation for the further understanding of the biological functions of membrane proteins,the design and development of membrane-targeting polypeptide drugs,and the preparation of responsive biomaterials.