Analysis of thermodynamic determinants in helix propensities of nonpolar amino acids through a novel free energy calculation
Analysis of thermodynamic determinants in helix propensities of nonpolar amino acids through a novel free energy calculation
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DOI：
10.1021/ja953347o
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发表时间：
1996-02-07
影响因子：
15
通讯作者：
Purisima, EO
中科院分区：
文献类型：
--
作者：
Wang, J;Purisima, EO
使用新的自由能模拟方法计算聚丙氨酸螺旋中心的Gly、Ala、瓦尔、Ile和Leu的相对螺旋倾向（Wang等人，J. Mol. Biol. 1995，253，473），其允许自由能分解成其各种热力学组分。计算的相对自由能变化与Chakrabartty等人（Protein Science 1994，3，843）关于丙氨酸基肽的最近的一组实验数据很好地一致。所产生的α-螺旋中的侧链旋转异构体分布也与基于蛋白质晶体结构的统计调查的文献中的报道一致。一个详细的分解的自由能表明，溶剂化效应，或特别是疏水性，有相对于甘氨酸的氨基酸的螺旋倾向的贡献不大。侧链-螺旋基质货车范德华相互作用通常是有利的，并且占螺旋折叠时相对于Gly的自由能变化的大部分。构型熵在相对自由能变化中起重要作用，但不是主导作用。计算了中心氨基酸在折叠过程中构型熵的绝对变化，这通常是很难估计的。限制螺旋基质中氨基酸主链的熵成本在25 ℃下为约1.5 kcal/mol，显著大于与螺旋中侧链熵减少相关的成本。
The relative helix propensities of Gly, Ala, Val, Ile, and Leu in the center of a polyalanine helix were calculated using a novel free energy simulation method (Wang et al. J. Mol. Biol. 1995, 253, 473) that permits the decomposition of the free energy into its various thermodynamic components. The calculated relative free energy changes agree well with the recent set of experimental data of Chakrabartty et al. (Protein Science 1994, 3, 843) on alanine-based peptides. The side chain rotamer distributions in the alpha-helix produced are also consistent with the reports in the literature based on a statistical survey of crystal structures of proteins. A detailed decomposition of the free energy showed that the solvation effect, or hydrophobicity in particular, has little contribution to the helix propensities of the amino acids relative to Gly. The side chain-helical matrix van der Waals interactions are generally favorable and account for a large part of the free energy change relative to Gly upon helix folding. The configurational entropy plays a significant, but not dominant, role in the relative free energy changes. The absolute change of configurational entropy of a central amino acid in folding, which is usually difficult to assess, was also obtained. The entropic cost of restricting the backbone of an amino acid in a helical matrix is about 1.5 kcal/mol at 25 degrees C, significantly larger than the cost associated with the reduction in side chain entropy in the helix.