Hajnic Matea, Osorio Juan I, Zagrovic Bojan
Department of Structural and Computational Biology, Max F. Perutz Laboratories, University of Vienna, Campus Vienna Biocenter 5, Vienna 1030, Austria.
Phys Chem Chem Phys. 2015 Sep 7;17(33):21414-22. doi: 10.1039/c5cp01486g. Epub 2015 Jul 29.
Despite the paramount importance of protein-nucleic acid interactions in different cellular processes, our understanding of such interactions at the atomistic level remains incomplete. We have used molecular dynamics (MD) simulations and 15 μs of sampling time to study the behavior of amino acids and amino-acid sidechain analogs in aqueous solutions of different mimetics of naturally occurring nucleobases, including dimethylpyridine (DMP) and unsubstituted purine and pyrimidine rings. By using structural and energetic analysis, we have derived preference scales for the interaction of amino acids and their sidechain analogs with different nucleobase mimetics and have exhaustively compared them with each other. A close correspondence with a standard hydrophobicity measure in the case of the pyrimidine mimetic DMP and purines suggests that the hydrophobic effect is the main defining factor behind such interactions. We analyze our findings in the context of the origin of the genetic code and the recently proposed cognate mRNA-protein complementarity hypothesis. Most importantly, we show that unsubstituted purine and pyrimidine rings alone cannot differentiate between predominantly purine- and pyrimidine-coded amino acids, suggesting that for such specificity to exist, it must primarily reside in ring substituents.
尽管蛋白质 - 核酸相互作用在不同细胞过程中至关重要，但我们对这种相互作用在原子水平上的理解仍不完整。我们利用分子动力学（MD）模拟和15微秒的采样时间，研究了氨基酸和氨基酸侧链类似物在不同天然存在的核碱基模拟物水溶液中的行为，这些模拟物包括二甲基吡啶（DMP）以及未取代的嘌呤和嘧啶环。通过结构和能量分析，我们得出了氨基酸及其侧链类似物与不同核碱基模拟物相互作用的偏好尺度，并对它们进行了详尽的相互比较。嘧啶模拟物DMP和嘌呤与标准疏水性测量结果的密切对应表明，疏水效应是此类相互作用背后的主要决定性因素。我们在遗传密码起源和最近提出的同源mRNA - 蛋白质互补性假说的背景下分析了我们的发现。最重要的是，我们表明仅未取代的嘌呤和嘧啶环无法区分主要由嘌呤和嘧啶编码的氨基酸，这表明要存在这种特异性，它必须主要存在于环取代基中。
