Ceruso M A, Grottesi A, Di Nola A
Department of Chemistry, University of Rome "La Sapienza," Rome, Italy.
Proteins. 1999 Sep 1;36(4):436-46. doi: 10.1002/(sici)1097-0134(19990901)36:4<436::aid-prot7>3.0.co;2-l.
The effects of core-packing on the structure, function and mechanics of the RNA-binding 4-helix-bundle Rop have been studied by molecular dynamics simulations. The structural, dynamical and geometrical properties of the Rop homodimer, (formed by the antiparallel juxtaposition of two helix-turn-helix motifs), have been compared with those of three protein variants described by Munson et al. (Protein Sci, 5:1584-1593, 1996), where the core of the native protein has been systematically repacked using a two-amino acid alphabet: Ala(2)Leu(2)-8, Ala(2)Leu(2)-8-rev, and Leu(2)Ala(2)-8. The results showed that it was possible to readily distinguish the inactive protein Leu(2)Ala(2)-8 from the other functionally active systems based on tertiary and quaternary structure criteria. Structural properties such as native secondary structure content did not correlate with biological activity. Biological activity was related in part to the relative arrangement of the residues within the binding site. But, more global aspects, related to the overall topology of the helical bundle, accounted for the small functional differences between Ala(2)Leu(2)-8 and Ala(2)Leu(2)-8-rev. Mechanically, the 4-helix-bundle absorbed core mutations by altering the local structure at the sequence termini and in the turns that join the two helices of each monomer, and by changing the overall orientation and separation of the extremely rigid helices. Proteins 1999;36:436-446.
通过分子动力学模拟研究了核心包装对RNA结合四螺旋束Rop的结构、功能和力学的影响。将Rop同二聚体（由两个螺旋-转角-螺旋基序反平行并列形成）的结构、动力学和几何性质与Munson等人（《蛋白质科学》，5:1584 - 1593，1996）描述的三种蛋白质变体进行了比较，其中天然蛋白质的核心已使用双氨基酸字母表进行系统重新包装：Ala(2)Leu(2)-8、Ala(2)Leu(2)-8-rev和Leu(2)Ala(2)-8。结果表明，基于三级和四级结构标准，可以很容易地将无活性的蛋白质Leu(2)Ala(2)-8与其他功能活性系统区分开来。天然二级结构含量等结构性质与生物活性不相关。生物活性部分与结合位点内残基的相对排列有关。但是，与螺旋束整体拓扑相关的更全局方面，解释了Ala(2)Leu(2)-8和Ala(2)Leu(2)-8-rev之间微小的功能差异。在力学上，四螺旋束通过改变序列末端和连接每个单体两个螺旋的转角处的局部结构，以及通过改变极其刚性的螺旋的整体取向和间距来吸收核心突变。《蛋白质》1999年；36:436 - 446。
