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Noncovalent Interactions between Unsolvated Peptides

机译:未溶解的肽之间的非共价相互作用

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摘要

The conformations of the unsolvated dimers and trimers produced by electrospraying mixtures of polyalanine-based peptides have been examined using ion mobility measurements in conjunction with molecular dynamics simulations. These multimers can provide models for how the secondary structure associates into the motifs that makeup the tertiary structure domains of proteins. Mixtures of helix-forming monomers (Ac-A_(14)K and Ac-A_(15)K and Ac-(GA)_7K and Ac-A(GA)_7K; Ac = acetyl, G = glycine, A = alanine, and K = lysine) yield V-shaped helical dimers where the C termini are tethered together by the protonated lysine side chain from one peptide interacting with the C terminus of the other (exchanged lysines). Trimers from the Ac-(GA)_7K and Ac-A(GA)_7K mixture adopt a pinwheel arrangement of helices with all three C termini tethered together by exchanged lysines. Trimers are much less abundant for the Ac-A_(14)K and Ac-A_(15)K mixture. The V-shaped dimer and pinwheel trimer arrangement leads to a cooperative electrostatic stabilization of the helices through the interaction of the combined charge with the helix dipoles. Mixtures of globule-forming monomers (Ac-K(GA)_7 and Ac-KA(GA)_7_ form predominantly globular multimers. In some conformations, however, the helical state is stabilized by interactions with the local environment. Examples include the antiparallel arrangement of helices that is present as a minor component for the Ac-K(GA)_7·Ac-KA-(GA)_7 + 2H~+ dimer and dominant for the Ac-KA_(14)·Ac-KA_(15) + 2H~+ dimer, as well as conformations with one or more helices which occur for the trimers from the Ac-K(GA)_7 and Ac-KA(GA)_7 mixture.
机译:电喷雾聚丙氨酸肽的混合物产生的未溶剂化二聚体和三聚体的构象已通过离子迁移率测量和分子动力学模拟进行了检验。这些多聚体可为二级结构如何与构成蛋白质三级结构域的基序相关联提供模型。螺旋形成单体(Ac-A_(14)K和Ac-A_(15)K以及Ac-(GA)_7K和Ac-A(GA)_7K的混合物; Ac =乙酰基,G =甘氨酸,A =丙氨酸, ;和K =赖氨酸)产生V形螺旋二聚体,其中C末端由一个肽与另一个C末端(交换的赖氨酸)相互作用的质子化赖氨酸侧链束缚在一起。 Ac-(GA)_7K和Ac-A(GA)_7K混合物的三聚体采用螺旋形的风车排列,所有三个C末端均由交换的赖氨酸束缚在一起。对于Ac-A_(14)K和Ac-A_(15)K混合物,三聚体的含量要低得多。通过组合电荷与螺旋偶极子的相互作用,V形二聚体和风车三叶草的布置导致了螺旋的协同静电稳定作用。形成球状单体(Ac-K(GA)_7和Ac-KA(GA)_7_)的混合物主要形成球状多聚体,但在某些构型中,螺旋态通过与局部环境的相互作用而稳定化。作为Ac-K(GA)_7·Ac-KA-(GA)_7 + 2H〜+二聚体的次要成分存在且对Ac-KA_(14)·Ac-KA_(15)+起主导作用的螺旋2H〜+二聚体,以及来自Ac-K(GA)_7和Ac-KA(GA)_7混合物的三聚体的一种或多种螺旋构象。

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