Revisiting the Ramachandran plot:: Hard-sphere repulsion, electrostatics, and H-bonding in the α-helix
Revisiting the Ramachandran plot:: Hard-sphere repulsion, electrostatics, and H-bonding in the α-helix
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DOI：
10.1110/ps.03235203
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发表时间：
2003-11-01
期刊：
影响因子：
8
通讯作者：
Brasseur, R
中科院分区：
文献类型：
--
作者：
Ho, BK;Thomas, A;Brasseur, R
是什么决定了Ramachandran图中允许区域的形状？尽管Ramachandran用1-4硬球斥力解释了这些区域，但与数据存在差异，特别是α (R), α (L)和β链区域是对角的。α (R)区也沿α -螺旋变化，在中心和氨基端受到限制，但在羧基端扩散。通过分析蛋白质结构的高分辨率数据库，我们发现Ramachandran标准立体图中的某些1-4硬球排斥不影响统计分布。忽略这些空间冲突(N…Hi+l和i-l…C)，我们确定了一组修正的空间冲突(C- β…O, Oi-l……倪+ l, C-beta……Ni+ 1, i- 1, c - 1, i- 1…O)与数据产生更好的匹配。我们还发现Ramachandran图中的严格禁止区域被多个空间冲突排除，而异常区域仅被一个显著空间冲突排除。然而，空间冲突本身并不能解释对角线区域。利用静电学分析了特定原子间相互作用的构象依赖性，我们发现α (R)和α (L)-区域的对角线形状也取决于N…Hi+l和Oi-l…C相互作用，对角β链区域是由于CO和NH偶极子的排列。最后，我们在一个仅使用氢键约束的简单模型中再现了沿着α -螺旋的Ramachandran图的变化。这使我们能够根据主链熵来合理化α -螺旋的氨基端和羧基端之间的差异。
What determines the shape of the allowed regions in the Ramachandran plot? Although Ramachandran explained these regions in terms of 1-4 hard-sphere repulsions, there are discrepancies with the data where, in particular, the alpha(R), alpha(L), and beta-strand regions are diagonal. The alpha(R)-region also varies along the alpha-helix where it is constrained at the center and the amino terminus but diffuse at the carboxyl terminus. By analyzing a high-resolution database of protein structures, we find that certain 1-4 hard-sphere repulsions in the standard steric map of Ramachandran do not affect the statistical distributions. By ignoring these steric clashes (N...Hi+l and Oi-l...C), we identify a revised set of steric clashes (C-beta...O, Oi-l...Ni+l, C-beta...Ni+l, Oi-l...C-beta, and Oi-l...O) that produce a better match with the data. We also find that the strictly forbidden region in the Ramachandran plot is excluded by multiple steric clashes, whereas the outlier region is excluded by only one significant steric clash. However, steric clashes alone do not account for the diagonal regions. Using electrostatics to analyze the conformational dependence of specific interatomic interactions, we find that the diagonal shape of the alpha(R) and alpha(L)-regions also depends on the optimization of the N...Hi+l and Oi-l...C interactions, and the diagonal beta-strand region is due to the alignment of the CO and NH dipoles. Finally, we reproduce the variation of the Ramachandran plot along the alpha-helix in a simple model that uses only H-bonding constraints. This allows us to rationalize the difference between the amino terminus and the carboxyl terminus of the alpha-helix in terms of backbone entropy.