Srinivasan J, Leclerc F, Xu W, Ellington A D, Cedergren R
Département de Biochimie, Université de Montréal, Québec, Canada.
Fold Des. 1996;1(6):463-72. doi: 10.1016/S1359-0278(96)00062-4.
In spite of the great interest in the interaction between RNAs and proteins, no general protocol for modelling these complexes is presently available. This methodological vacuum is particularly acute because the structure of few such complexes is known.
A general strategy for docking and modelling RNA-protein complexes has been developed. The docking procedure involves minimizing electrostatic and van der Waals' interaction energies of conformationally rigid structures during docking. After docking, libraries of amino acid sidechain conformations are searched to obtain the best interactions between the peptide and the RNA. Using this method, we have reproduced the structure of a bovine immunodeficiency virus (BIV) Tat peptide bound to BIV TAR RNA and have developed a model for the structure of the arginine-rich HIV-1 Rev peptide (Rev34-50) interacting with the Rev-binding element (RBE).
The resulting model of the Rev34-50-RBE complex predicts that although no single arginine sidechain is responsible for complex formation, residues Arg2, Arg5 and Arg11 are more important for binding than the other arginine residues in the peptide. One model is supported by binding measurements performed on wild-type and mutant RBE molecules with the peptide.
尽管人们对RNA与蛋白质之间的相互作用极为关注，但目前尚无用于模拟这些复合物的通用方案。由于已知的此类复合物结构很少，这种方法学上的空白尤为突出。
已开发出一种对接和模拟RNA - 蛋白质复合物的通用策略。对接过程包括在对接期间使构象刚性结构的静电和范德华相互作用能最小化。对接后，搜索氨基酸侧链构象文库以获得肽与RNA之间的最佳相互作用。使用这种方法，我们重现了与BIV TAR RNA结合的牛免疫缺陷病毒（BIV）Tat肽的结构，并建立了富含精氨酸的HIV - 1 Rev肽（Rev34 - 50）与Rev结合元件（RBE）相互作用的结构模型。
所得的Rev34 - 50 - RBE复合物模型预测，虽然没有单个精氨酸侧链负责复合物的形成，但肽中的Arg2、Arg5和Arg11残基在结合方面比其他精氨酸残基更重要。通过对野生型和突变型RBE分子与该肽进行结合测量，支持了一种模型。
