Podlogar B L, Leo G C, McDonnell P A, Loughney D A, Caldwell G W, Barrett J F
R. W. Johnson Pharmaceutical Research Institute, Raritan, New Jersey 08869, USA.
J Med Chem. 1997 Oct 10;40(21):3453-5. doi: 10.1021/jm970156i.
A practical combination of comparative modeling and NMR spectroscopy was used to generate a three-dimensional structure of the response regulator protein, Spo0F. The backbone structure obtained compares to the Spo0F Y13S mutant X-ray structure with an rmsd of 2.0 A. We provide results which suggest that structures obtained by this method are suitable for drug discovery. The results of the GRID and DOCK methods as applied to the model and X-ray structures of Spo0F are remarkably similar and tend to suggest the same design conclusions. This trend is illustrated by these same techniques applied to two experimentally derived structures of the analogous protein, CheY, which exhibit a pairwise rmsdBB on the same order as that found for the two Spo0F structures.
采用比较建模和核磁共振光谱学的实用组合方法生成了应答调节蛋白Spo0F的三维结构。所得的主链结构与Spo0F Y13S突变体的X射线结构相比，均方根偏差为2.0 Å。我们提供的结果表明，通过该方法获得的结构适用于药物发现。应用于Spo0F模型和X射线结构的GRID和DOCK方法的结果非常相似，并且倾向于得出相同的设计结论。将这些相同技术应用于类似蛋白CheY的两个实验推导结构时也呈现出这种趋势，这两个CheY结构之间的主链均方根偏差与两个Spo0F结构之间的偏差处于同一量级。
