DRUG BINDING TO UNUSUAL DNA STRUCTURES

我们正在研究特殊的分子识别 DNA结构，如平行双链体、三链体和四链体 通过小分子。 有证据表明，这些 体内可能存在不同类型的结构， 药物开发的目标。 我们发现了一种配体 与[d（G4T4G4）]2四链体的特异性复合物，并且具有 用2D NMR测定了其溶液结构。 我们已经出版了 DOCK在发现RNA特异性配体中的应用 主沟。 我们的大部分结构确定工作以及 基于DOCK的调查在很大程度上依赖于MidasPlus的使用。 为 例如，对我们所有的结构进行目视检查， 使用MidasPlus，它可以提供非常有用的距离和角度 任何结构的信息。 能够与多个 不同的分子是至关重要的，在评估结合 一个分子与另一个分子的结合，就像我们在配体与 四链体和RNA双链体。

We are investigating the specific molecular recognition of unusual DNA structures such as parallel duplexes, triplexes and quadruplexes by small molecules. There is some evidence suggesting that these types of structures may exist in vivo and they may represent unique targets for drug development. We have identified a ligand that forms a specific complex with the [d(G4T4G4)]2 quadruplex and have determined its solution structure using 2D NMR. We have published the application of DOCK to the discovery of ligands specific for the RNA major groove. Much of our structure determination work as well as DOCK-based investigations relies heavily on the use of MidasPlus. For example, visual examination of all of our structures is carried out with MidasPlus, which can provide very helpful distance and angle information for any structure. The ability to work with several different molecules is of crucial importance in evaluating the binding of one molecule to another, as in our work on ligand binding to quadruplexes and RNA duplexes.