Short-range conformational energies, secondary structure propensities, and recognition of correct sequence-structure matches
Short-range conformational energies, secondary structure propensities, and recognition of correct sequence-structure matches
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DOI：
10.1002/(sici)1097-0134(199711)29:3
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发表时间：
1997-11-01
期刊：
影响因子：
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通讯作者：
Jernigan, RL
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文献类型：
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作者：
Bahar, I;Kaplan, M;Jernigan, RL
对已知结构进行统计分析，以评估短程能量考虑的效用。对于每种类型的氨基酸，导出了控制（1）虚拟 C-α-C-α 键的扭转和键角变化以及（2）扭转和键角变化之间的耦合的电势。每个残基对天然蛋白质的稳定性贡献大约 -2 RT，其中大约一半是由于偶联效应。不同残基的α螺旋态的扭转势被证实与溶剂暴露区域的单位点突变的自由能变化测量密切相关。同样，尽管三级背景在稳定β-折叠方面发挥着作用，但不同氨基酸的β-折叠势和自由能测量的尺度之间显示出令人满意的相关性。此外，我们的α-螺旋态残基特异性势与其他基于热力学的尺度之间存在极好的一致性。使用反向折叠协议进行的线程实验表明，62 个测试结构中有 50 个基于短程电位正确识别了它们的天然序列。在同时考虑连续远距离残基之间的短程势和非键相互作用势时，性能提高到 55。已知沿一级结构的近残基之间的相互作用，即局部或短程相互作用，单独用于理解蛋白质的三级结构偏好是不够的。然而，短程构象势的知识可以使二级结构倾向合理化，并有助于区分正确和不正确的三级折叠。 (C) 1997 Wiley-Liss, Inc.
A statistical analysis of known structures is made for an assessment of the utility of short-range energy considerations. For each type of amino acid, the potentials governing (1) the torsions and bond angle changes of virtual C-alpha-C-alpha bonds and (2) the coupling between torsion and bond angle changes are derived. These contribute approximately -2 RT per residue to the stability of native proteins, approximately half of which is due to coupling effects. The torsional potentials for the alpha-helical states of different residues are verified to be strongly correlated with the free-energy change measurements made upon single-site mutations at solvent-exposed regions, Likewise, a satisfactory correlation is shown between the beta-sheet potentials of different amino acids and the scales from free-energy measurements, despite the role of tertiary context in stabilizing beta-sheets. Furthermore, there is excellent agreement between our residue-specific potentials for alpha-helical state and other thermodynamic based scales. Threading experiments performed by using an inverse folding protocol show that 50 of 62 test structures correctly recognize their native sequence on the basis of short-range potentials. The performance is improved to 55, upon simultaneous consideration of short-range potentials and the nonbonded interaction potentials between sequentially distant residues, Interactions between near residues along the primary structure, i.e., the local or short-range interactions, are known to be insufficient, alone, for understanding the tertiary structural preferences of proteins alone. Yet, knowledge of short-range conformational potentials permits rationalizing the secondary structure propensities and aids in the discrimination between correct and incorrect tertiary folds. (C) 1997 Wiley-Liss, Inc.