INFLUENCES OF SOLVENT WATER ON PROTEIN FOLDING - FREE-ENERGIES OF SOLVATION OF CIS AND TRANS PEPTIDES ARE NEARLY IDENTICAL
INFLUENCES OF SOLVENT WATER ON PROTEIN FOLDING - FREE-ENERGIES OF SOLVATION OF CIS AND TRANS PEPTIDES ARE NEARLY IDENTICAL
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DOI：
10.1021/bi00412a047
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发表时间：
1988-06-14
期刊：
影响因子：
2.9
通讯作者：
WOLFENDEN, R
中科院分区：
文献类型：
--
作者：
RADZICKA, A;PEDERSEN, L;WOLFENDEN, R
肽键与水的相互作用如此强烈，以至于它们的顺式和反式异构体的溶剂化自由能之间的微小差异都可能对蛋白质结构产生重大影响。然而，在氘代溶剂中高稀释度下的质子磁共振研究表明，N-甲基甲酰胺以顺式异构体的形式存在，在水中为8%，在氯仿中为10.3%，在苯中为8.8%，在环己烷中为9.2%。质子和碳共振的积分强度表明，N-甲基乙酰胺在水中以顺式异构体的形式存在，其含量仅为1.5%，在非极性溶剂中变化不大。使用6- 31 G ** 基组的量子力学计算以合理的精度再现了这些相对丰度，并表明对于任一酰胺，顺式和反式异构体的偶极矩之间几乎没有差异。顺式/反式平衡对溶剂环境的显着不敏感性和反式异构体的大量优势，无论环境的极性如何（约100%）。98.5%的N-甲基乙酰胺，其性质可能类似于典型的肽键），这与在球状蛋白的三维结构中一贯观察到的肽键对反式构型的压倒性偏好雅阁。
Peptide bonds interact so strongly with water that even a modest difference between the free energies of solvation of their cis and trans isomers could have a significant bearing on protein structure. However, proton magnetic resonance studies at high dilution in deuteriated solvents show that N-methylformamide exists as the cis isomer to the extent of 8% in water, 10.3% in chloroform, 8.8% in benzene, and 9.2% in cyclohexane. Integrated intensities of proton and carbon resonances show that N-methylacetamide exists as the cis isomer to the extent of only 1.5% in water, no changing much in nonpolar solvents. Quantum mechanical calculations using the 6-31G** basis set reproduce these relative abundances with reasonable accuracy and show that there is little difference between the dipole moments of the cis and trans isomers for either amide. The remarkable insensitivity of cis/trans equilibria to the solvent environment and the heavy preponderance of trans isomers regardless of the polarity of the surroundings (ca. 98.5% for N-methylacetamide, whose properties may resemble those of a typical peptide bond) accord with the overwhelming preference of peptide bonds for the trans configuration that is consistently observed in the three-dimensional structures of globular proteins.