RULES OF ALPHA HELIX FORMATION

本项目的长期目标是定量地了解 肽在水中形成α-螺旋的机制。 这意味 能够预测任何肽形成的螺旋的数量 由一个给定的氨基酸序列。 这对健康的重要性 工作是了解蛋白质折叠的机制，这是一个 生物医学研究中最基本的问题。 α-螺旋的研究 形成代表了最简单的蛋白质折叠分析， 最基本的水平。 可以得到精确的物理化学答案， 询问有关折叠机制的问题。 的主要决定因素 已知肽螺旋形成是螺旋和N-帽倾向 20种氨基酸和螺旋稳定的相互作用 特定侧链对之间。 取得了长足进展 最近，在测量20种氨基酸的螺旋和N-帽倾向方面， 在水中 这项建议的具体目标如下。 第一，衡量 三氟乙醇-水混合物中的这些参数，用于与 在水中测定的值，以帮助考虑到螺旋 在蛋白质中，一半暴露在水里，一半被埋在地下， 水 第二，合成其序列对应于 蛋白质中的螺旋区域，并比较预测和观察到的 这些肽的螺旋含量。 第三，测量两类螺旋- 稳定的侧链相互作用：氢键形成的特定 侧链对，以及由各种对形成的疏水相互作用 非极性链。

The long-term objective of this project is to understand quantitatively the mechanism of alpha-helix formation by peptides in water. This means being able to predict for any peptide the amount of helix that is formed by a given amino acid sequence. The health-related significance of this work is to understand the mechanism of protein folding, which is one of the most basic problems in biomedical research. The study of alpha-helix formation represents the analysis of protein folding at its simplest and most fundamental level. Exact physico-chemical answers can be obtained to questions asked about the mechanism of folding. The main determinants of peptide helix formation are known to be the helix and N-cap propensities of the 20 amino acids and the helix-stabilizing interactions that occur between specific pairs of side chains. Rapid progress has been made recently in measuring helix and N-cap propensities of the 20 amino acids in water. The specific aims of this proposal are as follows. First, to measure these parameters in trifluoroethanol-water mixtures, for comparison with values determined in water, to help take account of the fact that helices in proteins are half exposed to water and half buried, out of contact with water. Second, to synthesize peptides whose sequences correspond to helical regions in proteins, and to compare the predicted and observed helix contents of these peptides. Third, to measure two classes of helix- stabilizing side-chain interactions: hydrogen bonds formed by specific pairs of side chains, and hydrophobic interactions formed by various pairs of nonpolar chains.