Department of Chemistry, Chicago Center for Theoretical Chemistry, The University of Chicago, Chicago, Illinois 60637, United States.
Department of Chemistry, Indiana University, Bloomington, Indiana 47405, United States.
J Phys Chem A. 2023 Aug 3;127(30):6282-6291. doi: 10.1021/acs.jpca.3c03744. Epub 2023 Jul 25.
Ion mobility spectrometry-mass spectrometry and quantum chemical calculations are used to determine the structures and stabilities of the singly protonated peptide HKPGG. The two peaks making up the IMS distribution are shown to be tautomers differing by the location of the extra proton on either the lysine side chain or the N-terminus. The lysine-protonated tautomer is strongly preferred entropically while being disfavored in terms of the electronic energy and enthalpy. This relationship is shown, through comparison of all low-lying conformers of both tautomers, to be related to the strong hydrogen-bond network of the N-terminally protonated tautomer. A general relationship is demonstrated wherein stronger cross-peptide hydrogen-bond networks result in entropically disfavored conformers. Further effects of the HKPGG hydrogen-bond network are probed by computationally examining singly and doubly methylated analogues. These results demonstrate the importance of the entropic consequences of hydrogen bonds to peptide stability as well as techniques for perturbing the hydrogen-bond network and folding preferences of peptides via minimal chemical modification.
离子淌度质谱和量子化学计算被用于确定 HKPGG 单质子化肽的结构和稳定性。组成 IMS 分布的两个峰被证明是互变异构体，区别在于额外质子在赖氨酸侧链或 N 末端的位置。赖氨酸质子化互变异构体在熵方面具有强烈的优势，而在电子能量和焓方面则处于不利地位。通过比较两种互变异构体的所有低能构象，这种关系表明与 N 末端质子化互变异构体的强氢键网络有关。证明了一个普遍的关系，即更强的跨肽氢键网络导致熵不利的构象。通过计算检查单甲基化和双甲基化类似物进一步研究了 HKPGG 氢键网络的影响。这些结果表明氢键对肽稳定性的熵效应以及通过最小化学修饰干扰氢键网络和肽折叠偏好的技术的重要性。
