Molecular Mechanism of the Effects of Salt and pH on the Affinity between Protein A and Human Immunoglobulin G1 Revealed by Molecular Simulations
Protein A from the bacterium Staphylococcus aureus (SpA) has been widely used as an affinity ligand for purification of immunoglobulin G (IgG).The affinity between SpA and IgG is affected differently by salt and pH,but their molecular mechanisms still remain unclear.In this work,molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area analysis were performed to investigate the salt (NaCl) and pH effects on the affinity between SpA and human IgG1 (MgG1).It is found that salt and pH affect the interactions of the hot spots of SpAby different mechanisms.In the salt solution,the compensations between helices Ⅰ and Ⅱ of SpA as well as between the nonpolar and dectrostatic energies make the binding free energy independent of salt concentration.At pH 3.0,the unfavorable electrostatic interactions increase greatly and become the driving force for dissociation of the SpA-hIgG1 complex.They mainly come from the strong dectrostatic repulsions between positively charged residues (H137,R146,and K154) of SpA and the positively charged residues of hIgG1.It is considered to be the molecular basis for hIgG1 elution from SpA-based affinity adsorbents at pH 3.0.The dissociation mechanism is then used to refine the binding model of SpA to hIgG1.The model is expected to help design high-affinity peptide ligands of IgG.
Bo Huang Fu-Feng Liu Xiao-Yan Dong Yan Sun
Department of Biological Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
国际会议
南京
英文
361-370
2012-05-13（万方平台首次上网日期，不代表论文的发表时间）