The flexing/twirling helix: Exploring the flexibility about molecular hinges formed by proline and glycine motifs in transmembrane helices
The flexing/twirling helix: Exploring the flexibility about molecular hinges formed by proline and glycine motifs in transmembrane helices
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DOI：
10.1021/jp026686u
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发表时间：
2003-01-16
影响因子：
3.3
通讯作者：
Sansom, MSP
中科院分区：
文献类型：
--
作者：
Bright, JN;Sansom, MSP
脯氨酸，甘氨酸，和这些残基的组合在跨膜α-螺旋从膜蛋白的重要性已被强调在最近的研究中，其中可能的功能作用已被确定。在这项研究中，我们建立在这样的工作，通过分子动力学模拟系统地追求序列和构象性质之间的关系。我们模拟了24个不同的序列基序，涉及脯氨酸和甘氨酸配对的“主机”多聚丙氨酸螺旋嵌入在溶剂化的辛烷板作为膜模拟。比较了不同基序之间的柔性和构象动力学。我们发现，脯氨酸是必要的，以引入显着的弯曲/扭结旋转运动的肽，作为一个有效的“分子铰链”，使前和后脯氨酸部分的螺旋。虽然适度的灵活性，甚至发现在聚丙氨酸螺旋和甘氨酸残基略有明显，脯氨酸产生最大的扰动，从规范的行为，并引入各向异性到扭结旋转空间的肽。这种行为对给定基序的依赖性可能在解释现有数据和预测给定序列的灵活性以及暗示可能的功能作用方面都很重要。
The importance of prolines, glycines, and combinations of these residues in transmembrane alpha-helices from membrane proteins has been highlighted in recent studies in which possible functional roles have been identified. In this study we build on such work by systematically pursuing the relationship between sequence and conformational properties via molecular dynamics simulation. We simulate 24 different sequence motifs involving proline and glycine pairings in a "host" polyalanine helix embedded in a solvated octane slab as a membrane mimetic. The flexibility and conformational dynamics are compared between the different motifs. We find that a proline is necessary to introduce pronounced bend/kink-swivel motions in the peptide, acting as an effective "molecular hinge" that decouples the pre- and post-proline portions of the helix. Although moderate flexibility is found in even a polyalanine helix and is pronounced slightly by glycine residues, proline produces the greatest perturbation from canonical behavior and introduces anisostropy into the kink-swivel space of the peptide. The dependence of this behavior on the given motif may be important both in interpreting existing data and in predicting the flexibility of a given sequence and suggesting possible functional roles.