Astbury Centre for Structural Molecular Biology , University of Leeds , Leeds LS2 9JT , U.K.
J Phys Chem B. 2018 Dec 13;122(49):11784-11791. doi: 10.1021/acs.jpcb.8b08344. Epub 2018 Oct 23.
Helices are the most common structural pattern observed in structured proteins. Polypeptide sequences that form helices in isolation have been identified and extensively studied. These are generally rich in alanine, the amino acid with strongest helical propensity. Insertion of charged or polar amino acids has been shown to be necessary to make alanine-rich peptides soluble and sometimes even increase the helicity of the peptides. More recently sequences that contain mostly charged residues (E-R/K rich) have been found in naturally occurring proteins that are highly helical, soluble, and extended regardless their length. Artificial sequences composed mostly or exclusively of charged amino acids have been designed that are also highly helical, depending on the specific pattern of oppositely charged residues. Here we explore the thermodynamic properties of a number of 16-residue long peptides with varying helical propensity by performing equilibrium simulations over a broad range of temperatures. We observe quantitative differences in the peptides' helical propensities that can be related to qualitative differences in the free energy landscape, depending on the ampholytic patterns in the sequence. The results provide hints on how the specific physical properties of naturally occurring long sequences with similar patterns of charged residues may relate to their biological function.
螺旋是在结构蛋白中观察到的最常见的结构模式。已经鉴定并广泛研究了在分离状态下形成螺旋的多肽序列。这些序列通常富含丙氨酸，丙氨酸是具有最强螺旋倾向的氨基酸。插入带电荷或极性氨基酸已被证明对于使富含丙氨酸的肽可溶是必要的，有时甚至可以增加肽的螺旋度。最近，在天然存在的高度螺旋、可溶和伸展的蛋白质中发现了含有大多数带电荷残基（富含 E-R/K）的序列，无论其长度如何。已经设计了由大多数或完全由带电荷氨基酸组成的人工序列，这些序列也具有高度的螺旋性，这取决于相反电荷残基的特定模式。在这里，我们通过在较宽的温度范围内进行平衡模拟，研究了许多具有不同螺旋倾向的 16 个残基长肽的热力学性质。我们观察到肽的螺旋倾向存在定量差异，这可以与自由能景观中的定性差异相关，具体取决于序列中的两性模式。这些结果提示了具有相似电荷残基模式的天然存在的长序列的特定物理性质如何与其生物学功能相关。
