Breed J, Kerr I D, Sankararamakrishnan R, Sansom M S
Laboratory of Molecular Biophysics, University of Oxford, England.
Biopolymers. 1995 Jun;35(6):639-55. doi: 10.1002/bip.360350610.
alpha-Aminoisobutyric acid (Aib) is a helicogenic alpha, alpha-dimethyl amino acid found in channel-forming peptaibols such as alamethicin. Possible effects of Aib on helix-helix packing are analyzed. Simulated annealing via restrained molecular dynamics is used to generate ensembles of approximately parallel helix dimers. Analysis of variations in geometrical and energetic parameters within ensembles defines how tightly a pair of helices interact. Simple hydrophobic helix dimers are compared: Ala20, Leu20, Aib20, and P20, the latter a simple channel-forming peptide [G. Menestrina, K.P. Voges, G. Jung, and G. Boheim (1986) Journal of Membrane Biology, Vol. 93, pp. 111-132]. Ala20 and Leu20 dimers exhibit well-defined ridges-in-grooves packing with helix crossing angles (omega) of the order of +20 degrees. Aib20 alpha-helix dimers are much more loosely packed, as evidenced by a wide range of omega values and small helix-helix interaction energies. However, when in a 3(10) conformation Aib20 helices pack in three well-defined parallel modes, with omega ca. -15 degrees, +5 degrees, and 10 degrees. Comparison of helix-helix interaction energies suggests that dimerization may favor the 3(10) conformation. P20, with 8 Aib residues, also shows looser packing of alpha-helices. The results of these studies of hydrophobic helix dimers are analyzed in the context of the ridges-in-grooves packing model. Simulations are extended to dimers of alamethicin, and of an alamethicin derivative in which all Aib residues are replaced by Leu. This substitution has little effect on helix-helix packing. Rather, such interactions appear to be sensitive to interactions between polar side chains. Overall, the results suggest that Aib may modulate the packing of simple hydrophobic helices, in favor of looser interactions. For more complex amphipathic helices, interactions between polar side chains may be more critical.
α-氨基异丁酸（Aib）是一种可形成螺旋的α,α-二甲基氨基酸，存在于诸如短杆菌肽之类的形成通道的肽抗生素中。分析了Aib对螺旋-螺旋堆积的可能影响。通过受限分子动力学进行模拟退火，以生成近似平行的螺旋二聚体集合。对集合内几何和能量参数变化的分析确定了一对螺旋相互作用的紧密程度。比较了简单的疏水螺旋二聚体：Ala20、Leu20、Aib20和P20，后者是一种简单的形成通道的肽[G.梅内斯特里纳、K.P.沃格斯、G.荣格和G.博海姆（1986年）《膜生物学杂志》，第93卷，第111 - 132页]。Ala20和Leu20二聚体表现出明确的脊-槽堆积，螺旋交叉角（ω）约为+20度。Aib20α-螺旋二聚体堆积得更为松散，这由广泛的ω值和小的螺旋-螺旋相互作用能证明。然而，当处于3(10)构象时，Aib20螺旋以三种明确的平行模式堆积，ω约为 - 15度、+5度和10度。螺旋-螺旋相互作用能的比较表明二聚化可能有利于3(10)构象。含有8个Aib残基的P20也显示出α-螺旋堆积较松散。在脊-槽堆积模型的背景下分析了这些疏水螺旋二聚体研究的结果。模拟扩展到短杆菌肽二聚体，以及一种所有Aib残基都被Leu取代的短杆菌肽衍生物。这种取代对螺旋-螺旋堆积几乎没有影响。相反，这种相互作用似乎对极性侧链之间的相互作用敏感。总体而言，结果表明Aib可能调节简单疏水螺旋的堆积，有利于更松散的相互作用。对于更复杂的两亲性螺旋，极性侧链之间的相互作用可能更关键。
