Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 16610 Prague 6, Czech Republic.
J Phys Chem B. 2013 Jul 11;117(27):8150-8. doi: 10.1021/jp405683s. Epub 2013 Jul 1.
Ion-specific effects on salting-in and salting-out of proteins, protein denaturation, as well as enzymatic activity are typically rationalized in terms of the Hofmeister series. Here, we demonstrate by means of NMR spectroscopy and molecular dynamics simulations that the traditional explanation of the Hofmeister ordering of ions in terms of their bulk hydration properties is inadequate. Using triglycine as a model system, we show that the Hofmeister series for anions changes from a direct to a reversed series upon uncapping the N-terminus. Weakly hydrated anions, such as iodide and thiocyanate, interact with the peptide bond, while strongly hydrated anions like sulfate are repelled from it. In contrast, reversed order in interactions of anions is observed at the positively charged, uncapped N-terminus, and by analogy, this should also be the case at side chains of positively charged amino acids. These results demonstrate that the specific chemical and physical properties of peptides and proteins play a fundamental role in ion-specific effects. The present study thus provides a molecular rationalization of Hofmeister ordering for the anions. It also provides a route for tuning these interactions by titration or mutation of basic amino acid residues on the protein surface.
离子的特性对蛋白质的盐析和盐溶、蛋白质变性以及酶活性的影响通常可以用豪夫迈斯特序列来解释。在这里，我们通过 NMR 光谱和分子动力学模拟表明，用离子在本体水中的水合性质来解释豪夫迈斯特离子排序的传统解释是不充分的。使用三肽作为模型系统，我们表明，当 N 端去帽时，对于阴离子的豪夫迈斯特序列从直接序列变为反转序列。弱水合阴离子，如碘离子和硫氰酸根离子，与肽键相互作用，而强水合阴离子，如硫酸根离子，被排斥。相反，在带正电荷的未被掩蔽的 N 端观察到阴离子相互作用的反转顺序，并且类似地，在带正电荷的氨基酸侧链上也应该是这种情况。这些结果表明，肽和蛋白质的特定化学和物理性质在离子特异性效应中起着根本作用。因此，本研究为阴离子的豪夫迈斯特排序提供了分子合理化解释。它还为通过在蛋白质表面滴定或突变碱性氨基酸残基来调节这些相互作用提供了一种途径。
