Virtual Screening and Structure Generation Applied to Drug Design

The methods of computer-aided drug design can be divided into two categories according to whether or not the structures of receptors are known1, corresponding to two principal strategies: (1) searching the bio-active ligands against virtual combinatorial libraries and calculating the affinity energy between ligand and receptor by docking ; (2) QSAR and 3D-structure data-mining. 3D-QSAR method is now applied widely to drug discovery, but this method is generally limited to refine the structu…     

Interaction of Phenylpropanoid Glycosides with Nucleotides and DNA:Kinetic and Molecular Modeling Study

Phenylpropanoid glycosides (PPGs) are substances extracted from Pedicularis. They have been largely studied for their interesting biological and pharmacological properties^[1-3], in particular, their double role in the protection of DNA:preventing the DNA bases from radical attack, and rapidly repairing damaged DNA^[4-6]. A series of kinetic measurements has been performed with different deoxynucleotide radicals. Two major remakes can be done from the experimental results:(1) the reactivity of PPGs seems to depend on the number of phenolic hydroxyl groups; (2) the reactivity depends upon the positions of these groups. These observations are in agreements with the experiments performed on tumour cells.     

基于分子对接的苯丙素甙（PPGs）类化合物的虚拟筛选和合理设计

采用虚拟化合物生成法对抗肿瘤的苯丙素甙(PPGs)类化合物进行了配体受体对 接研究。以三种不同的骨架结构为基础分别生成了五十个虚拟苯丙素甙(PPGs)类化 合物，并将它们与端粒DNA受体进行分子对接，分析已知结构的对接结果，通过虚 拟筛选的方法得到了一批与受体相互作用能较高并且复合物能量较低的新的有潜力 的活性化合物。该方法可以弥补分子对接研究中，只能计算药物与受体的相互作用 ，无法有效设计新化合物的不足。这种方法在基于结构的药物分子设计中具有重要 的意义。