STRUCTURE DEPENDENT PKA SHIFTS

最近，Urry等人，报道了大的pKa位移的电荷 谷氨酸组与组成的变化， 聚[Fv（IPGVG），Fe（IPGEG）]家族的聚五肽（PPP） （其中摩尔分数fv和fe满足关系fv + fe = 1）。 实验确定的滴定曲线清楚地表明两个 关于Fe的制度：Fe > 0.65和fE< 0.65。 第一规程 被作者称为静电制度和 第二个是疏水区。 他们特别发现， 静电诱导的pKa位移不如 在纯水和0.15N NaCl水溶液中疏水诱导的pKa。 这一系列公私伙伴关系被提议采用折叠β螺旋 每圈大约有三个五聚体， β-匝用作螺旋匝之间的间隔物。 根据 对作者来说，这种折叠结构导致了 与Glu侧链非常接近的疏水残基 五肽中第4位的残基。 这些 Urry假设分子内相互作用依赖于结构， et.例如，主要负责实验观察到的pKa PPP和相关肽中Glu移位。 为了测试他们的 假设，我们进行了一系列计算，其中PPP 被建模为Fe = 0.11的9个五聚体的集合;即，与 序列（IPGVG）4（IPGEG）（IPGVG）4。 我们的理论结果为 pKa位移与实验值符合得很好， 为所观察到的pKa的拟定分子基础提供了支持 这种类型多肽中的移位。

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.