STRUCTURE DEPENDENT PKA SHIFTS

最近，Urry等人报道了PKA的大变化 谷氨酸基团与蛋白质组成变化的关系 多聚五肽(PPP)家族[Fv(IPGVG)，Fe(IPGEG)] (其中摩尔分数Fv和Fe满足关系Fv+Fe= 1)。实验测定的滴定曲线清楚地显示出两条 与铁有关的制度：铁和铁0.65和铁和铁0.65。第一个政权 被作者称为静电状态，而 第二种是疏水状态。特别是，他们发现 静电诱导的pKa漂移没有静电引起的pKa漂移大 疏水诱导的pKA在纯水和0.15N氯化钠水中。 这一系列的PPP已被提议采用折叠的β螺旋 每轮大约有三个五聚体的构象， 贝塔转数充当螺旋转弯之间的间隔物。根据 对作者来说，这种折叠结构导致了 谷氨酸侧链附近的疏水残基 五肽中第4位的残基。这些 Urry假设了依赖于结构的分子内相互作用， 埃特。Al.主要负责实验观察到的pKa PPP及相关多肽中谷氨酸的移位。为了测试他们的 假设，我们进行了一系列计算，其中购买力平价 被建模为9个五聚体的集合，其中fe=0.11；即， 序列(IPGVG)4(IPGEG)(IPGVG)4.我们的理论结果 PKa漂移与实验值吻合较好。 为所观察到的pKA的分子基础提供支持 这种类型的多肽的转变。

Recently Urry, et.al., reported large pKa shifts of charged glutamic acid groups associated with changes of composition in polypentapeptides (PPP) of the family poly[fv(IPGVG), fe(IPGEG)] (where the mole fractions fv and fe satisfied the relation fv + fe = 1). The experimentally determined titration curve clearly shows two regimes with respect to fe : fe > 0.65 and fE< 0.65. The first regime is referred to by the authors as the electrostatic regime and the second one as the hydrophobic regime. In particular, they found that the electrostatic-induced pKa shift is not as large as the hydrophobic-induced pKa in both pure water and aqueous 0.15N NaCl. This familyof PPPs has been proposed to adopt a folded beta-spiral conformation with approximately three pentamers per turn, wi th beta-turns acting as spacers between turns of the spiral. According to the authors, this folded structure leads to an arrangement of hydrophobic residues in close proximity to the side chains of Glu residues at position 4th in the pentapeptides. These structure-dependent intramolecular interactions were assumed by Urry, et. al., to be mainly responsible for the experimentally observed pKa shift of Glu in PPP and related peptides. In order to test their assumption, we carried out a series of calculations in which the PPP was modeled as a collection of 9 pentamers with fe = 0.11; i.e., with the sequence (IPGVG)4 (IPGEG) (IPGVG)4. Our theoretical result for the pKa shift is in good agreement with the experimental value and provides support for the proposed molecular basis for the observed pKa shift in this type of polypeptide.