不同pH值下聚合物点（Pdots）与卵清蛋白的结合亲和力
Binding Affinity between Polymer Dots (Pdots) and Ovalbumin Protein at Varying pH
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中文总结 AI 辅助
本研究通过全原子分子动力学模拟，探究不同pH值下PFBT与PSMA组成的Pdots和卵清蛋白的结合亲和力，发现pH=1时二者结合亲和力优于pH=7，静电相互作用是关键因素。
中文摘要 AI 辅助
确定聚合物点（Pdots）与蛋白质之间的结合机制，对于开发生物医学和生物成像领域的新型纳米技术具有重要意义。本研究采用全原子分子动力学模拟，测定了pH=7和pH=1条件下Pdots与卵清蛋白的结合亲和力。所选Pdots为聚[(9,9-二辛基芴-2,7-二基)-alt-共-(1,4-苯并-(2,1',3)-噻二唑)]（PFBT）与聚（苯乙烯/马来酸酐）（PSMA）的混合物，组成比例可变。在pH=7时，Pdots因PFBT上的COO-官能团带有净负电荷，蛋白质也呈净负电荷；在pH=1时，Pdots呈电中性，PFBT仅含COOH官能团，蛋白质则带有净正电荷。研究通过改变蛋白质的初始位置，使其处于立方体的全部6个取向，以此对蛋白质的初始位置进行采样；对每个取向，将蛋白质向Pdots的PFBT区域牵拉，比较6种不同相互作用面及两种选定pH值下的库仑相互作用能和 Lennard-Jones（LJ）相互作用能。结果显示，12种情况的LJ相互作用能相近；测得的库仑相互作用能表明，pH=1时的结合亲和力优于pH=7；沿牵拉坐标的平均力势（PMF）随pH值变化，pH=1时6种初始构型中有2种的PMF为负值，而pH=7时无负值，证实pH=1时结合亲和力更优；pH=1时其中一个面的PMF最低，约为-30 kcal/mol，远低于pH=7时最低情况的约6 kcal/mol。对pH=7和pH=1条件下蛋白质残基电荷分布的比较进一步表明，静电相互作用对结合亲和力至关重要，pH=7时带负电荷的残基减少，无法与带负电荷的Pdots结合。
英文摘要
Determining the binding mechanisms between polymer dots and proteins is important for developing novel nanotechnologies for biomedicine and bioimaging. In this work, we use all-atom molecular dynamics simulations to determine the binding affinity of Pdots with ovalbumin protein at pH = 7 and 1. The selected Pdots are mixtures of Poly[(9,9-dioctylfluorenyl-2,7-diyl)-alt-co-(1,4-benzo-(2,1',3)-thiadiazole)] (PFBT) and poly(styrene/maleic anhydride) (PSMA) with varying composition. At pH = 7, the Pdots have a net negative charge due to the COO- functional groups on the PFBT, and the protein also has a net negative charge. At pH = 1, the Pdots are charge neutral with PFBT containing only COOH functional groups, and the protein also has a net positive charge. We sample the initial position of the protein by varying its initial position through all 6 orientations of a cube. For each orientation, we pull the protein towards the PFBT region of the Pdot. We compare the Coulombic and Lennard-Jones interaction energies for the 6 different interacting faces and two selected pH values. We find that the LJ interaction energies are similar among all 12 of these cases. The measured Coulombic interaction energies suggest that pH = 1 has better binding affinity than pH = 7. The potentials of mean force (PMF) along the pulling coordinates differ with pH. The PMFs from 2 of the 6 initial configurations at pH = 1 are negative whereas none of them are negative at pH = 7, confirming the preferred binding affinity when pH = 1. One of the faces at pH = 1 has the lowest PMF of about -30 kcal/mol, which is much lower than about 6 kcal/mol seen for the lowest case at pH = 7. Comparison of protein residue charge distributions at pH = 7 and 1 further shows that the electrostatic interaction is critical to the binding affinity, and negatively charged residues reduce at pH = 7 does not bind to negatively charged Pdot.
