Reyes C M, Kollman P A
Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, 94122-0446, USA.
J Mol Biol. 2000 Apr 14;297(5):1145-58. doi: 10.1006/jmbi.2000.3629.
An adaptive binding mechanism, requiring large conformational rearrangements, occurs commonly with many RNA-protein associations. To explore this process of reorganization, we have investigated the conformational change upon spliceosomal U1A-RNA binding with molecular dynamics (MD) simulations and free energy analyses. We computed the energetic cost of conformational change in U1A-hairpin and U1A-internal loop binding using a hybrid of molecular mechanics and continuum solvent methods. Encouragingly, in all four free energy comparisons (two slightly different proteins, two different RNAs), the free macromolecule was more stable than the bound form by the physically reasonable value of approximately 10 kcal/mol. We calculated the absolute binding free energies for both complexes to be in the same range as that found experimentally.
一种需要大量构象重排的适应性结合机制，常见于许多RNA与蛋白质的相互作用中。为了探究这种重组过程，我们利用分子动力学（MD）模拟和自由能分析，研究了剪接体U1A与RNA结合时的构象变化。我们采用分子力学和连续介质溶剂方法相结合的方式，计算了U1A - 发夹结构和U1A - 内环结合中构象变化的能量代价。令人鼓舞的是，在所有四项自由能比较中（两种略有不同的蛋白质，两种不同的RNA），自由大分子比结合形式更稳定，其合理的物理值约为10千卡/摩尔。我们计算出两种复合物的绝对结合自由能与实验值处于同一范围。
