多重正则算法预测核糖核酸酶A C肽的三级结构
Tertiary structure prediction of C-peptide of ribonuclease A by multicanonical algorithm
摘要：
我们对核糖核酸酶A的C肽进行了多重正则蒙特卡罗模拟。通过CD和NMR实验已知，该肽在水溶液中具有高α-螺旋含量，并且残基Glu-2 $^-$和His-12 $^+$的侧链电荷在α-螺旋的稳定性中起重要作用。为了证实这些实验的影响，我们使用了两个类似物的肽与带电和中性侧链的Glu-2和His-12。两个介电函数，距离依赖性和常数，被认为是研究溶剂的贡献的影响。所有的模拟都是从随机的初始构象开始的。计算了各种热力学量，如平均螺旋度作为残基数的函数和两个侧链之间的平均距离作为温度的函数。计算结果与圆二色谱和核磁共振实验的结果一致。获得的最低能量构象具有从Ala-4到Gln-11的α-螺旋，与从核糖核酸酶A的X射线晶体学实验中推导出的相应结构完全一致。结果表明，Glu-2 $^-$和Arg-10 $^+$侧链间的盐桥（NMR和X-射线实验均证实存在）仅在侧链适当带电时形成。它的形成大大增强时，使用的距离相关的介电函数。
英文摘要：
We have performed multicanonical Monte Carlo simulations of C-peptide of ribonuclease A. It is known by CD and NMR experiments that this peptide has high alpha-helix content in aqueous solution and that the side-chain charges of residues Glu-2$^-$ and His-12$^+$ play an important role in the stability of the alpha-helix. In order to confirm these experimental implications, we have used two analogues of the peptide with charged and neutral side chains of Glu-2 and His-12. Two dielectric functions, distance-dependent and constant, are considered to study the effects of solvent contributions. All the simulations were started from random initial conformations. Various thermodynamic quantities such as average helicity as a function of residue number and average distance between two side chains as a function of temperature are calculated. The results are found to be in accord with the implications of CD and NMR experiments. The lowest-energy conformation obtained has an alpha-helix from Ala-4 to Gln-11 in complete agreement with the corresponding structure deduced from an X-ray crystallography experiment of ribonuclease A. It is shown that the salt bridge between the side chains of Glu-2$^-$ and Arg-10$^+$, which is known to exist from both NMR and X-ray experiments, is formed only when the side chains are properly charged. Its formation is greatly enhanced when the distance-dependent dielectric function is used.
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