Positional preference of proline in α-helices
Positional preference of proline in α-helices
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DOI：
10.1110/ps.8.7.1492
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发表时间：
1999-07-01
期刊：
影响因子：
8
通讯作者：
Kang, YK
中科院分区：
文献类型：
--
作者：
Kim, MK;Kang, YK
对序列为Ac-（Ala）（n）-Pro-（Ala）（m）-NHMe（n + m = 14）的含脯氨酸丙氨酸的十五肽进行了构象自由能计算，以确定脯氨酸在α-螺旋中的位置偏好。通过从α-螺旋构象的自由能中减去延伸构象的自由能来计算每种肽的相对自由能，其在此用作偏好的量度。发现在N-末端具有脯氨酸的肽的倾向最高（即，Ncap + 1位置），并且在Ncap、N'（Ncap - 1）和C'（Ccap + 1）位置发现了下一个倾向。这些计算结果与从蛋白质的X射线结构估计的位置倾向是合理一致的。脯氨酸周围的氢键断裂被发现在不稳定的α-螺旋构象中起作用，然而，这提供了相应的N-H和C = O基团的有利的水合作用。脯氨酸在α-螺旋开始处的最高偏好似乎是由于脯氨酸之前的两个残基之间的有利的静电能和非键合能以及脯氨酸残基本身的α-螺旋构象的内在稳定性以及脯氨酸对α-螺旋的氢键没有干扰。计算了α-螺旋中Pro取代Ala的平均自由能变化为4.6 kcal/mol，与寡肽二聚体和芽孢杆菌RNA酶及T4溶菌酶蛋白质的实验值（约4 kcal/mol）相吻合。
Conformational free energy calculations have been carried out for proline-containing alanine-based pentadecapeptides with the sequence Ac-(Ala)(n)-Pro-(Ala)(m)-NHMe, where n + m = 14, to figure out the positional preference of proline in alpha-helices. The relative free energy of each peptide was calculated by subtracting the free energy of the extended conformation from that of the alpha-helical one, which is used here as a measure of preference. The highest propensity is found for the peptide with proline at the N-terminus (i.e., Ncap + 1 position), and the next propensities are found at Ncap, N' (Ncap - 1), and C' (Ccap + 1) positions. These computed results are reasonably consistent with the positional propensities estimated from X-ray structures of proteins. The breaking in hydrogen bonds around proline is found to play a role in destabilizing alpha-helical conformations, which, however, provides the favored hydration of the corresponding N-H and C = O groups. The highest preference of proline at the beginning of alpha-helix appears to be due to the favored electrostatic and nonbonded energies between two residues preceding proline and the intrinsic stability of alpha-helical conformation of the proline residue itself as well as no disturbance in hydrogen bonds of alpha-helix by proline. The average free energy change for the substitution of Ala by Pro in a alpha-helix is computed to be 4.6 kcal/mol, which is in good agreement with the experimental value of similar to 4 kcal/mol estimated for an oligopeptide dimer and proteins of barnase and T4 lysozyme.