Zytkiewicz Emily, Shkel Irina A, Cheng Xian, Rupanya Anuchit, McClure Kate, Karim Rezwana, Yang Sumin, Yang Felix, Record M Thomas
Department of Biochemistry, University of Wisconsin - Madison, Madison, Wisconsin 53706.
Biophysics Program, University of Wisconsin - Madison, Madison, Wisconsin 53706.
bioRxiv. 2023 Jul 17:2023.07.12.548600. doi: 10.1101/2023.07.12.548600.
In addition to amide hydrogen bonds and the hydrophobic effect, interactions involving π-bonded sp atoms of amides, aromatics and other groups occur in protein self-assembly processes including folding, oligomerization and condensate formation. These interactions also occur in aqueous solutions of amide and aromatic compounds, where they can be quantified. Previous analysis of thermodynamic coefficients quantifying net-favorable interactions of amide compounds with other amides and aromatics revealed that interactions of amide sp O with amide sp N unified atoms (presumably C=O···H-N hydrogen bonds) and amide/aromatic sp C (lone pair-π, n-π ) are particularly favorable. Sp C-sp C (hydrophobic), sp C-sp C (hydrophobic, CH-π), sp C-sp C (hydrophobic, π-π) and sp C-sp N interactions are favorable, sp C-sp N interactions are neutral, while sp O-sp O and sp N-sp N self-interactions and sp O-sp C interactions are unfavorable. Here, from determinations of favorable effects of fourteen amides on naphthalene solubility at 10, 25 and 45 °C, we dissect amide-aromatic interaction free energies into enthalpic and entropic contributions and find these vary systematically with amide composition. Analysis of these results yields enthalpic and entropic contributions to intrinsic strengths of interactions of amide sp O, sp N, sp C and sp C unified atoms with aromatic sp C atoms. For each interaction, enthalpic and entropic contributions have the same sign and are much larger in magnitude than the interaction free energy itself. The amide sp O-aromatic sp C interaction is enthalpy-driven and entropically unfavorable, consistent with direct chemical interaction (e.g. lone pair-π) while amide sp C- and sp C-aromatic sp C interactions are entropy-driven and enthalpically unfavorable, consistent with hydrophobic effects. These findings are relevant for interactions involving π-bonded sp atoms in protein processes.
除了酰胺氢键和疏水作用外，在蛋白质自组装过程（包括折叠、寡聚化和凝聚物形成）中，还会发生涉及酰胺、芳香族和其他基团的π键合sp原子的相互作用。这些相互作用也发生在酰胺和芳香族化合物的水溶液中，在那里它们可以被量化。先前对量化酰胺化合物与其他酰胺和芳香族化合物净有利相互作用的热力学系数的分析表明，酰胺sp O与酰胺sp N统一原子（推测为C=O···H-N氢键）以及酰胺/芳香族sp C（孤对-π，n-π）的相互作用特别有利。Sp C-sp C（疏水）、sp C-sp C（疏水，CH-π）、sp C-sp C（疏水，π-π）和sp C-sp N相互作用是有利的，sp C-sp N相互作用是中性的，而sp O-sp O和sp N-sp N自相互作用以及sp O-sp C相互作用是不利的。在这里，通过测定14种酰胺在10、25和45℃下对萘溶解度的有利影响，我们将酰胺-芳香族相互作用自由能分解为焓和熵的贡献，并发现这些贡献随酰胺组成而系统变化。对这些结果的分析得出了酰胺sp O、sp N、sp C和sp C统一原子与芳香族sp C原子相互作用内在强度的焓和熵贡献。对于每种相互作用，焓和熵贡献具有相同的符号，并且在大小上比相互作用自由能本身大得多。酰胺sp O-芳香族sp C相互作用是焓驱动的且熵不利的，这与直接化学相互作用（例如孤对-π）一致，而酰胺sp C-和sp C-芳香族sp C相互作用是熵驱动的且焓不利的，这与疏水作用一致。这些发现与蛋白质过程中涉及π键合sp原子的相互作用相关。
