Helix, sheet, and polyproline II frequencies and strong nearest neighbor effects in a restricted coil library
Helix, sheet, and polyproline II frequencies and strong nearest neighbor effects in a restricted coil library
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DOI：
10.1021/bi0474822
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发表时间：
2005-07-19
期刊：
影响因子：
2.9
通讯作者：
Freed, KF
中科院分区：
文献类型：
--
作者：
Jha, AK;Colubri, A;Freed, KF
蛋白质折叠的一个核心问题是每个残基的主链构象偏好在多大程度上稳定了天然状态。我们研究了每个氨基酸在非规则二级结构条件下的构象偏好。在这个庞大但高度受限的线圈库中，主链优先采用与脯氨酸II构象一致的二面角，而不是α或β构象。对聚脯氨酸II构象的偏好与溶剂化程度无关。结合一种新的掩蔽程序，我们线圈库中的频率准确地概括了结构区域中氨基酸的螺旋和片频率，以及聚脯氨酸II倾向。因此，α -螺旋和β -薄片的结构倾向以及未折叠肽中脯氨酸II构象的结构倾向只能通过局部效应来合理化。此外，这些倾向往往受到化学性质和邻近残基构象的强烈影响，这与Flory孤立残基假说相反。
A central issue in protein folding is the degree to which each residue's backbone conformational preferences stabilize the native state. We have studied the conformational preferences of each amino acid when the amino acid is not constrained to be in a regular secondary structure. In this large but highly restricted coil library, the backbone preferentially adopts dihedral angles consistent with the polyproline II conformation rather than alpha or beta conformations. The preference for the polyproline II conformation is independent of the degree of solvation. In conjunction with a new masking procedure, the frequencies in our coil library accurately recapitulate both helix and sheet frequencies for the amino acids in structured regions, as well as polyproline II propensities. Therefore, structural propensities for alpha-helices and beta-sheets and for polyproline II conformations in unfolded peptides can be rationalized solely by local effects. In addition, these propensities are often strongly affected by both the chemical nature and the conformation of neighboring residues, contrary to the Flory isolated residue hypothesis.