Role of pK(A) in Charge Regulation and Conformation of Various Peptide Sequences.
Role of pK(A) in Charge Regulation and Conformation of Various Peptide Sequences.
复制标题
DOI：
10.3390/polym13020214
复制
发表时间：
2021-01-09
期刊：
影响因子：
5
通讯作者：
Košovan P
中科院分区：
文献类型：
--
作者：
Lunkad R;Murmiliuk A;Tošner Z;Štěpánek M;Košovan P
含有具有可电离侧链的氨基酸的肽代表弱两性电解质的典型实例，即具有多个可滴定酸和碱基团的分子，其通常在pH变化时表现出电荷调节性质。两性电解质上的带电基团彼此静电相互作用，并且它们的相互作用与（大）分子的构象偶联，导致复杂的反馈环。它们的电荷调节特性主要由单个可电离侧链决定，由带电基团之间的静电相互作用调节。后者由肽链中的氨基酸序列决定。在我们以前的工作中，我们介绍了一个简单的粗粒度模型的柔性肽。我们对实验进行了验证，证明了其能够定量预测各种肽在广泛的pH值范围内的电荷。在目前的工作中，我们研究了两种类型的肽序列：二嵌段和交替，它们中的每一个由相同数量的氨基酸与酸和碱侧链组成。我们发现，改变序列，同时保持相同的整体组成对构象有深远的影响，而它实际上并不影响肽的总电荷。尽管如此，序列显着影响个别群体的电荷状态，表明对总电荷的零净效应是意外取消效果的结果。此外，我们研究了酸和碱侧链之间的差异如何影响肽的电荷和构象，表明可以通过以下基于和氨基酸序列的简单指导原则来调节电荷调节特性。我们目前的研究结果提供了一个理论基础，为理解复杂的耦合之间的电离和构象的灵活的两性聚电解质，包括合成聚合物，仿生材料和生物分子，如内在无序的蛋白质，其功能可以通过调节pH值的变化。
Peptides containing amino acids with ionisable side chains represent a typical example of weak ampholytes, that is, molecules with multiple titratable acid and base groups, which generally exhibit charge regulating properties upon changes in pH. Charged groups on an ampholyte interact electrostatically with each other, and their interaction is coupled to conformation of the (macro)molecule, resulting in a complex feedback loop. Their charge-regulating properties are primarily determined by the of individual ionisable side-chains, modulated by electrostatic interactions between the charged groups. The latter is determined by the amino acid sequence in the peptide chain. In our previous work we introduced a simple coarse-grained model of a flexible peptide. We validated it against experiments, demonstrating its ability to quantitatively predict charge on various peptides in a broad range of pH. In the current work, we investigated two types of peptide sequences: diblock and alternating, each of them consisting of an equal number of amino acids with acid and base side-chains. We showed that changing the sequence while keeping the same overall composition has a profound effect on the conformation, whereas it practically does not affect total charge on the peptide. Nevertheless, the sequence significantly affects the charge state of individual groups, showing that the zero net effect on the total charge is a consequence of unexpected cancellation of effects. Furthermore, we investigated how the difference between the of acid and base side chains affects the charge and conformation of the peptide, showing that it is possible to tune the charge-regulating properties by following simple guiding principles based on the and on the amino acid sequence. Our current results provide a theoretical basis for understanding of the complex coupling between the ionisation and conformation in flexible polyampholytes, including synthetic polymers, biomimetic materials and biological molecules, such as intrinsically disordered proteins, whose function can be regulated by changes in the pH.
登录
查看更多内容
影响因子：
5
作者：
Blanco, Pablo M.;Madurga, Sergio;Garces, Josep L.
通讯作者：
Garces, Josep L.
影响因子：
3.9
作者：
de Vos, Wiebe M.;Leermakers, Frans A. M.;Kleijn, J. Mieke
通讯作者：
Kleijn, J. Mieke
影响因子：
4.6
作者：
Biehl, Philip;von der Luhe, Moritz;Schacher, Felix H.
通讯作者：
Schacher, Felix H.
影响因子：
16.6
作者：
Chang LW;Lytle TK;Radhakrishna M;Madinya JJ;Vélez J;Sing CE;Perry SL
通讯作者：
Perry SL
影响因子：
3.3
作者：
Hazra, Milan Kumar;Levy, Yaakov
通讯作者：
Levy, Yaakov