MOLECULAR MODELLING AND DRUG DESIGN BY COMPUTER

一种成功的模拟酶底物的方法已经活跃起来。 类比分析。这涉及到对药效团的识别和使用 搜索NCI DIS 3D数据库。 建模研究对两种广泛使用的分子建模的验证 计划已经完成并出版。然后选择了其中的一个 以建立NCI DIS 3D数据库。 酶结合已经证明，柔性配体，即药物，是 绑定到活动站点时发生变形。这一过程的能源审计 已经确立了它的热力学原理。 蛋白激酶C是蛋白激酶C中的药效团 确定并用作搜索NCI 3D数据库的目标。这些 研究已经发现了许多化合物，它们是这方面的抑制剂。 它们与佛波尔竞争PKC的活性部位。 与该酶结合的酪氨酸蛋白激酶底物利用 酪氨酸磷酸和多达10个疏水相互作用。是这样的 相互作用没有很好的记录，因此已经被研究过了。 它们很弱，但无处不在，人们认为它们可能会发挥作用 在酶识别其底物的过程中。 其他酶是活性类似物，已被证明对蛋白质有效 激酶C正被应用于其他几种酶，它们被认为是 为控制癌症或艾滋病提供化疗靶点。他们 包括HIV蛋白水解酶、HIV整合酶和端粒酶。

A successful approach to modeling of enzyme substrates has been active analog analysis. This involves identification and use of pharmacophores to search the NCI DIS 3D database. Modeling Studies Validation of two widely used molecular modeling programs has been completed and published. One of these was then selected to build the NCI DIS 3D database. Enzyme Binding It has been shown that flexible ligands, i.e. drugs, are deformed when binding to an active site. Energy audits of this process have established its thermodynamic rationale. Protein Kinase C The pharmacophore in protein kinase C has been identified and used as a target in searches of the NCI 3D database. These searches have produced numerous compounds which are inhibitors in that they compete with phorbol for the active site in PKC. Tyrosine Protein Kinase Substrate binding to this enzyme utilize a tyrosine phosphate and as many as 10 hydrophobic interactions. Such interactions are not well documented and they have therefore been studied. They are weak but ubiquitous and it is thought that they may play a role in the process by which an enzyme recognizes its substrates. Other Enzymes The active analog which has proved successful with protein kinase C is being applied to several other enzymes which are thought to offer chemotherapeutic targets for control of cancer or AIDS. They include HIV protease, HIV integrase and telomerase.