Free energy determinants of secondary structure formation: I. alpha-Helices.
Free energy determinants of secondary structure formation: I. alpha-Helices.
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DOI：
10.1006/jmbi.1995.0502
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发表时间：
1995-09
影响因子：
5.6
通讯作者：
A. Yang;B. Honig
中科院分区：
文献类型：
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作者：
A. Yang;B. Honig
计算了聚l -丙氨酸螺旋圈跃迁的Zimm-Bragg参数s和sigma。理论方法包括使用CHARMM势函数评估线圈态和螺旋态的气相构象能，并使用各种连续体溶剂化模型计算溶剂化效应。然后将构象自由能纳入由Go等人开发的用于计算s和sigma的形式中。用有限差分泊松-玻尔兹曼（FDPB）方法处理溶剂效应时，计算得到的s和sigma值以及与螺旋形成相关的焓变与实验数据吻合较好。从单个自由能分量的角度分析了螺旋-线圈过渡的驱动力。氢键的形成对螺旋稳定性的贡献很小，因为内部氢键能在很大程度上被从水中去除极性基团所产生的大量自由能成本所抵消。在螺旋构象中固定主二面角的熵耗约为7 e.u./残基（室温下约为2 kcal/mol）。有利于螺旋形成的主要驱动力可能与相互作用有关，包括密实螺旋构象中增强的范德华相互作用和疏水效应。它们对螺旋态的贡献约为2千卡/摩尔。丙氨酸和甘氨酸之间螺旋倾向的差异主要归因于涉及C β的疏水和堆积相互作用，而甘氨酸在线圈状态下的构象自由度增加所产生的贡献较小。本文对螺旋形成的描述与先前关于三级结构形成的结论一致，这些结论表明疏水和紧密排列的相互作用提供了稳定性，而氢键的形成构成了结构约束，这是由于隐藏不满意的氢键基团所带来的高自由能成本所造成的。因此，α -螺旋形成可以看作是一种疏水坍塌的形式，受到极性基团暴露于溶剂或形成氢键的要求的限制。更一般地说，从这项研究看来，要使折叠模型成为现实，它必须适当地考虑多肽链的化学性质，特别是酰胺基团的溶剂化能量。
The Zimm-Bragg parameters s and sigma are calculated for the helix-coil transition of poly-L-alanine. The theoretical approach involves evaluating gas phase conformational energies for both coil and helical states using the CHARMM potential function and accounting for solvation effects with various continuum solvation models. Conformational free energies are then incorporated into a formalism developed by Go et al. for the calculation of s and sigma. Calculated values for both s and sigma as well as the enthalpy change associated with helix formation are in good agreement with experimental data when the Finite Difference Poisson-Boltzmann (FDPB) method is used to treat solvent effects. The driving force for the helix-coil transition is analyzed in terms of individual free energy components. Hydrogen bond formation is found to contribute little to helix stability because the internal hydrogen bonding energy is largely canceled by the large free energy cost associated with removing polar groups from water. The entropic cost associated with fixing backbone dihedral angles in the helical conformation is found to be approximately 7 e.u./residue (about 2 kcal/mol at room temperature). The major driving force favoring helix formation can be associated with interactions including enhanced van der Waals interactions in the close-packed helix conformation and the hydrophobic effect. These contribute about 2 kcal/mol favoring the helical state. The differences in helical propensities between alanine and glycine are attributed primarily to hydrophobic and packing interactions involving the C beta with a smaller contribution arising from increased conformational freedom for glycine in the coil state. The description of helix formation presented here is consistent with previous conclusions regarding tertiary structure formation which suggest that hydrophobic and close-packed interactions provide stability while hydrogen bond formation constitutes a structural constraint imposed by the high free energy cost associated with burying unsatisfied hydrogen bonding groups. alpha-Helix formation may thus be viewed as a form of hydrophobic collapse constrained by the requirement that polar groups be either exposed to solvent or form hydrogen bonds. More generally it appears from this study that for a folding model to be a realistic, it must properly account for the chemical nature of the polypeptide chain, particularly the solvation energetics of amide groups.