Energetics of codon-anticodon recognition on the small ribosomal subunit
Energetics of codon-anticodon recognition on the small ribosomal subunit
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DOI：
10.1021/bi061713i
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发表时间：
2007-01-09
期刊：
影响因子：
2.9
通讯作者：
Aqvist, Johan
中科院分区：
文献类型：
--
作者：
Almlof, Martin;Ander, Martin;Aqvist, Johan
最近核糖体小亚基的晶体结构使得用计算方法研究核糖体上密码子识别的详细能量学成为可能。用显式溶剂分子动力学模拟结合线性相互作用能(LIE)方法，分析了同源和近同源反密码子茎环与核糖体解码中心的结合，其中包含Phe、UUU和UUC密码子的mRNA。计算的结合自由能与实验结合常数非常吻合，并再现了第一和第二密码子位置的错配与摆动位置的错配的相对影响。模拟进一步预测，在与Phe UUU密码子的复合体中，Leu2反密码子茎环比Ser茎环稳定约10倍。研究还发现，核糖体显著增强了密码子-反密码子复合体在水溶液中的固有稳定性差异。对模拟的结构分析证实了先前提出的普遍保守的核苷酸A1492、A1493和G530在解码过程中的重要性。
Recent crystal structures of the small ribosomal subunit have made it possible to examine the detailed energetics of codon recognition on the ribosome by computational methods. The binding of cognate and near-cognate anticodon stem loops to the ribosome decoding center, with mRNA containing the Phe UUU and UUC codons, are analyzed here using explicit solvent molecular dynamics simulations together with the linear interaction energy (LIE) method. The calculated binding free energies are in excellent agreement with experimental binding constants and reproduce the relative effects of mismatches in the first and second codon position versus a mismatch at the wobble position. The simulations further predict that the Leu2 anticodon stem loop is about 10 times more stable than the Ser stem loop in complex with the Phe UUU codon. It is also found that the ribosome significantly enhances the intrinsic stability differences of codon-anticodon complexes in aqueous solution. Structural analysis of the simulations confirms the previously suggested importance of the universally conserved nucleotides A1492, A1493, and G530 in the decoding process.