Soga Shinji, Shirai Hiroki, Kobori Masato, Hirayama Noriaki
Molecular Medicine Research Laboratories, Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki, Japan.
J Chem Inf Model. 2008 Aug;48(8):1679-85. doi: 10.1021/ci800113c. Epub 2008 Jul 22.
The idea that there should be a specific site on a protein for a particular functional small molecule is widespread. It is, however, usually not so easy to understand what characteristics of the site determine the binding ability of the functional small molecule. We have focused on the concurrence rate of the 20 standard amino acids at such binding sites. In order to correlate the concurrence rate and the specific binding site, we have analyzed high-quality X-ray structures of complexes between proteins and small molecules. A novel index characterizing the binding site based on the concurrency rate has been introduced. Using this index we have identified that there is a specific concavity designated as a chemocavity where a specific group of small molecules, i.e., canonical molecular group, is highly inclined to be bound. This study has demonstrated that a chemocavity is reserved for a specific canonical molecular group, and the prevalent idea has been confirmed.
蛋白质上存在特定功能小分子的特定结合位点这一观点广为流传。然而，通常并不容易理解该位点的哪些特征决定了功能小分子的结合能力。我们聚焦于此类结合位点上20种标准氨基酸的并发率。为了关联并发率与特定结合位点，我们分析了蛋白质与小分子复合物的高质量X射线结构。引入了一种基于并发率表征结合位点的新指标。利用该指标，我们确定存在一个特定的凹陷，称为化学腔，特定的一组小分子，即标准分子基团，极有可能与之结合。这项研究表明，化学腔是为特定的标准分子基团保留的，这一普遍观点得到了证实。
