Physical reasons for the unusual alpha-helix stabilization afforded by charged or neutral polar residues in alanine-rich peptides.
Physical reasons for the unusual alpha-helix stabilization afforded by charged or neutral polar residues in alanine-rich peptides.
复制标题
富含丙氨酸的肽中带电或中性极性残基提供不寻常的α螺旋稳定化的物理原因。
DOI：
10.1073/pnas.240455797
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发表时间：
2000
影响因子：
11.1
通讯作者：
Scheraga,HA
中科院分区：
文献类型：
--
作者：
Vila,JA;Ripoll,DR;Scheraga,HA
我们已经进行了构象能计算的序列为Ac-AAAAAXAAAA-NH 2在水中，其中X代表赖氨酸或谷氨酰胺的丙氨酸为基础的共聚物，以确定潜在的来源的稳定性的丙氨酸为基础的多肽含有带电的或高度可溶性的极性残基的电荷-电荷相互作用的情况下。结果表明，可电离或中性极性残基引入到序列中，使它们可溶螯合水远离的CO和NH基团的骨干，从而使他们能够形成内部氢键。这种溶剂化效应决定了丙氨酸残基的构象偏好，从而改变了丙氨酸残基的构象倾向。尽管我们对特定的氨基酸序列进行了模拟，但我们的结果提供了对一些基本原理的理解，这些基本原理支配着这些短序列的折叠过程，而不依赖于引入何种残基使其可溶。此外，我们还通过模拟研究了体介电常数对这些肽的构象偏好的影响。广泛的构象Monte Carlo搜索上的末端封闭的10-mer和16-mer的丙氨酸均聚物在盐的情况下进行假设值为80，40，和2的溶剂的介电常数ε。我们的模拟表明，这些寡肽增加α-螺旋含量的溶剂的体积介电常数降低的明显趋势。这种行为主要是由于CO和NH基团暴露于水性溶剂的损失。实验证据表明，水中氨基酸的螺旋倾向在加入某些醇（如三氟乙醇）后急剧增加。我们的研究结果提供了一个可能的解释的机制，酒精/水的混合物影响的自由能的螺旋丙氨酸寡肽相对于非螺旋的。
We have carried out conformational energy calculations on alanine-based copolymers with the sequence Ac-AAAAAXAAAA-NH2in water, where X stands for lysine or glutamine, to identify the underlying source of stability of alanine-based polypeptides containing charged or highly soluble polar residues in the absence of charge–charge interactions. The results indicate that ionizable or neutral polar residues introduced into the sequence to make them soluble sequester the water away from the CO and NH groups of the backbone, thereby enabling them to form internal hydrogen bonds. This solvation effect dictates the conformational preference and, hence, modifies theconformational propensityof alanine residues. Even though we carried out simulations for specific amino acid sequences, our results provide an understanding of some of the basic principles that govern the process of folding of these short sequences independently of the kind of residues introduced to make them soluble. In addition, we have investigated through simulations the effect of the bulk dielectric constant on the conformational preferences of these peptides. Extensive conformational Monte Carlo searches on terminally blocked 10-mer and 16-mer homopolymers of alanine in the absence of salt were carried out assuming values for the dielectric constant of the solvent ɛ of 80, 40, and 2. Our simulations show a clear tendency of these oligopeptides to augment the α-helix content as the bulk dielectric constant of the solvent is lowered. This behavior is due mainly to a loss of exposure of the CO and NH groups to the aqueous solvent. Experimental evidence indicates that thehelical propensityof the amino acids in water shows a dramatic increase on addition of certain alcohols, such us trifluoroethanol. Our results provide a possible explanation of the mechanism by which alcohol/water mixtures affect the free energy of helical alanine oligopeptides relative to nonhelical ones.