Structure-based thermodynamic scale of alpha-helix propensities in amino acids.
Structure-based thermodynamic scale of alpha-helix propensities in amino acids.
复制标题
基于结构的氨基酸α螺旋倾向的热力学尺度。
DOI：
10.1021/bi961319s
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发表时间：
1996
期刊：
影响因子：
2.9
通讯作者：
Freire,E
中科院分区：
文献类型：
--
作者：
Luque,I;Mayorga,OL;Freire,E
折叠能量学的结构参数已被用于预测α-螺旋中暴露位置的单个氨基酸突变的影响。这些结果已被用于推导基于结构的氨基酸的α-螺旋倾向的热力学标度。对四个有结构和实验热力学数据的不同体系进行了基于结构的热力学分析： T4溶菌酶[BLaber等人]。书名/作者The−/[by]J.(1992年)J.Mol.Biol.227,560−568]，合成亮氨酸拉链[O‘Neil&Degrado(1990)Science 250,646−651]，以及合成肽[Lyu等人]。(1990年)科学250,669−673]。这些研究使所有处于未折叠状态的氨基酸的溶剂可及表面积(ASA)得以优化。结果表明，一组结构/热力学参数很好地解释了所有螺旋倾向性的实验数据。对于T4溶菌酶，其ΔG值预测值与实验值的绝对差值平均值为0.09kcal/m ol，对Barnase为0.14kcal/m ol，对合成盘管为0.11kcal/m o l，对合成肽为0.08kcal/m o l。此外，这种方法很好地预测了蛋白质的整体稳定性，并合理地解释了氨基酸之间α-螺旋倾向的差异。所有氨基酸的预测ΔG值与实验G值之间的良好一致性验证了这种结构参数在折叠或结合自由能计算中的使用。
A structural parameterization of the folding energetics has been used to predict the effect of single amino acid mutations at exposed locations in α-helices. The results have been used to derive a structure-based thermodynamic scale of α-helix propensities for amino acids. The structure-based thermodynamic analysis was performed for four different systems for which structural and experimental thermodynamic data are available: T4 lysozyme [Blaber et al. (1994)J.Mol.Biol.235, 600−624], barnase [Horovitz et al. (1992)J.Mol.Biol.227, 560−568], a synthetic leucine zipper [O'Neil & Degrado (1990)Science 250, 646−651], and a synthetic peptide [Lyu et al. (1990)Science 250, 669−673]. These studies have permitted the optimization of the set of solvent-accessible surface areas (ASA) for all amino acids in the unfolded state. It is shown that a single set of structure/thermodynamic parameters accounts well for all the experimental data sets of helix propensities. For T4 lysozyme, the average value of the absolute difference between predicted and experimental ΔGvalues is 0.09 kcal/mol, for barnase 0.14 kcal/mol, for the synthetic coiled-coil 0.11 kcal/mol, and for the synthetic peptide 0.08 kcal/mol. In addition, this approach predicts well the overall stability of the proteins and rationalizes the differences in α-helix propensities between amino acids. The excellent agreement observed between predicted and experimental ΔGvalues for all amino acids validates the use of this structural parameterization in free energy calculations for folding or binding.