pH-Independence of trialanine and the effects of termini blocking in short peptides: a combined vibrational, NMR, UVCD, and molecular dynamics study.
pH-Independence of trialanine and the effects of termini blocking in short peptides: a combined vibrational, NMR, UVCD, and molecular dynamics study.
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DOI：
10.1021/jp310466b
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发表时间：
2013-04-11
影响因子：
3.3
通讯作者：
Schweitzer-Stenner, Reinhard
中科院分区：
文献类型：
--
作者：
Toal, Siobhan;Meral, Derya;Verbaro, Daniel;Urbanc, Brigita;Schweitzer-Stenner, Reinhard
现在有几条证据很好地证明了大体上未折叠的多肽，以及特定的丙氨酸，对多聚脯氨酸II(PPII)构象有内在的偏好。然而，由于实验的局限性和系统的内在动力学，研究展开状态下的局域有序是复杂的，这在某些情况下从不同类型的实验中得到了不一致的结果。研究这些体系的一种方法是使用短模型多肽，特别是短丙氨酸多肽，众所周知，短丙氨酸多肽主要采样水溶液中的pPII结构。最近，他等人。(J.Am化学。SoC。2012,134,1571-1576)提出，由于末端效应的存在，即被研究的氨基酸残基与末端电荷之间的静电相互作用，未被阻断的三肽可能不适合于研究未折叠多肽的构象倾向。为了确定改变N-末端和C-末端的质子化状态是否影响三肽中中心氨基酸残基的构象多种多样，我们研究了未被阻断的三丙氨酸的pH依赖性和丙氨酸在丙氨酸二肽中的构象偏好。为此，我们测量并全局分析了酰胺I‘带轮廓和核磁共振J偶联常数。我们将构象分布描述为可分配给Ramachandran图的特定子空间的二维高斯分布的叠加。结果表明，质子化状态的改变几乎不影响三丙氨酸的构象系综，特别是pPII的含量(χpPII=0.84)。我们发现，与三丙氨酸相比，丙氨酸二肽的pPII含量略低(χpPII=0.74)，并且更容易让人想起未被阻断的甘氨酸-丙氨酸-甘氨酸模型肽。此外，由电子圆二色谱和核磁共振谱得到的构象灵敏Δε(T)和3J(HnHα)(T)数据的两态热力学分析表明，在所有质子化状态下，三丙氨酸的自由能分布是相似的。对所研究的多肽进行的MD模拟证实了这一观点，并进一步表明未被封闭的三丙氨酸周围的水合壳不受C-末端基团的质子化/去质子化的影响。相反，丙氨酸二肽显示中心残基周围的水密度降低，水化壳更无序，这降低了pPII倾向并缩短了采样构象的寿命。
Several lines of evidence now well establish that unfolded peptides in general, and alanine in specific, have an intrinsic preference for the polyproline II (pPII) conformation. Investigation of local order in the unfolded state is, however, complicated by experimental limitations and the inherent dynamics of the system, which has in some cases yielded inconsistent results from different types of experiments. One method of studying these systems is the use of short model peptides, and specifically short alanine peptides, known for predominantly sampling pPII structure in aqueous solution. Recently, He et al. (J. Am. Chem. Soc. 2012, 134, 1571–1576) proposed that unblocked tripeptides may not be suitable models for studying conformational propensities in unfolded peptides due to the presence of end effect, i.e. electrostatic interactions between investigated amino acid residues and terminal charges. To determine whether changing the protonation states of the N- and C-termini influence the conformational manifold of the central amino acid residue in tripeptides, we have examined the pH-dependence of unblocked trialanine and the conformational preferences of alanine in the alanine dipeptide. To this end, we measured and globally analyzed amide I’ band profiles and NMR J-coupling constants. We described conformational distributions as the superposition of two-dimensional Gaussian distributions assignable to specific sub-spaces of the Ramachandran plot. Results show that the conformational ensemble of trialanine as a whole, and the pPII content (χpPII=0.84) in particular, remain practically unaffected by changing the protonation state. We found that compared to trialanine, the alanine dipeptide has slightly lower pPII content (χpPII=0.74) and an ensemble more reminiscent of the unblocked Gly-Ala-Gly model peptide. In addition, a two-state thermodynamic analysis of the conformational sensitive Δε(T) and 3J(HNHα)(T) data obtained from electronic circular dichroism and H-NMR spectra indicate that the free energy landscape of trialanine is similar in all protonation states. MD simulations for the investigated peptides corroborate this notion and show further that the hydration shell around unblocked trialanine is unaffected by the protonation/deprotonation of the C-terminal group. In contrast, the alanine dipeptide shows a reduced water density around the central residue as well as a less ordered hydration shell, which decreases the pPII propensity and reduces the lifetime of sampled conformations.
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影响因子：
3.3
作者：
Eker, F;Cao, XL;Schweitzer-Stenner, R
通讯作者：
Schweitzer-Stenner, R
影响因子：
15
作者：
Chen, K;Liu, ZG;Kallenbach, NR
通讯作者：
Kallenbach, NR
影响因子：
15
作者：
BRANT, DA;FLORY, PJ
通讯作者：
FLORY, PJ
影响因子：
4.4
作者：
Gorbunov, RD;Kosov, DS;Stock, G
通讯作者：
Stock, G
影响因子：
3.4
作者：
Best, Robert B.;Buchete, Nicolae-Viorel;Hummer, Gerhard
通讯作者：
Hummer, Gerhard