FACTORS AFFECTING THE SECONDARY STRUCTURE IN PROTEINS

人们普遍认为蛋白质的氨基酸序列 决定了其最终的三维结构。 在等级制度中 看来，一级结构决定了有规律的重复二级结构 结构，然后折叠成三级结构。 研究人员 已经注意到某些氨基酸对给定的二级氨基酸有偏好 结构，并且已经开发了许多使用氨基酸的方案 从一级结构预测二级结构的偏好。 如果 氨基酸偏好是绝对的，那么蛋白质折叠问题 无疑会得到解决。 由于偏好不是绝对的，一 可以反向看待蛋白质折叠问题并提出问题：为什么 每种氨基酸是否存在于每种类型的二级结构中？ 如果这个 问题可以得到解答，我们可能就能很好地解决这个问题 蛋白质折叠问题，我们的前两个具体目标解决了这个问题 问题。 1. 我们建议研究特殊的氨基酸序列 根据氨基酸偏好预测处于一个二级结构中， 在另一个二级结构中发现的。 这些是有趣的 序列，因为它们证明了我们的预测失败 方法。 我们的工作假设是环境对于 确定氨基酸序列形成的二级结构。 我们 将合成特殊序列并遵循二级结构 作为溶剂系统的函数。 2. 我们建议研究一些氨基酸成核的假设 二级结构的形成，以及二级结构的延续 结构相对独立于氨基酸，直到继续 的结构被破坏。 容易形成α螺旋的序列或 溶液中的β链是众所周知的；我们可以诱导无关的氨基吗 酸来延续这个结构？ 3. 我们建议使用圆二色性来研究二次 当前感兴趣的蛋白质结构，并改进我们的系统 分析 CD 的二级结构。 这延续了我们长期以来的 对蛋白质光谱与其二级结构的联系感兴趣， 但重点大大减少。

It is generally accepted that the amino acid sequence of a protein determines its ultimate three-dimensional structure. In the hierarchic view, the primary structure determines regular repeating secondary structures, which in turn fold up into a tertiary structure. Researchers have noted the certain amino acids have a preference for a given secondary structure, and a number of schemes have been developed that use amino acid preferences to predict secondary structure from primary structure. If the amino acid preferences were absolute, then the protein folding problem would undoubtedly be solved. Since the preferences are not absolute, one can view the protein folding problem in reverse and ask the question: Why is each amino acid found in every type of secondary structure? If this question can be answered, we might be well on our way to solving the protein folding problem, and our first two specific aims deal with this question. 1. We propose to investigate exceptional sequences of amino acids that are predicted to be in one secondary structure from amino acid preferences, that are found in another secondary structure. These are the interesting sequences because they are the demonstrated failures of our prediction methods. Our working hypothesis is that the environment is important in determining the secondary structure formed by an amino acid sequence. We would synthesize exceptional sequences and follow the secondary structure as a function of solvent system. 2. We propose to investigate the hypothesis that a few amino acids nucleate the formation of a secondary structure, and that continuation of the structure is relatively independent of the amino acids until continuation of the structure is broken. Sequences that readily form an alpha-helix or beta-strand in solution are well known; can we induce indifferent amino acids to continue this structure? 3. We propose to use circular dichroism to investigate the secondary structure of proteins of current interest, and to improve our system of analyzing CD for secondary structure. This continues our longstanding interest in relating the spectra of proteins to their secondary structure, but with considerably reduced emphasis.