STRUCTURE BASED DESIGN: INHIBITOR OF HIV RT

昆茨小组活动主要涉及基于结构的 配基设计方法。我们对提取结构性产品感兴趣 具有高级算法的信息；计算机图形例程 显示结构；精细化程序；交互能量 具有最新势能函数的最小化；药物设计 Dock和COMBIDOCK等工具。我们已经开始了一个结对的项目 通过计算搜索实现有机合成(多样化)。 多样化，使用有机转型来生成一个大家族 指定起点的产品。试剂和/或 然后，可以使用我们的对接技术对生成的化合物进行筛选。 用于有机数据库检索的DOCK软件包 假设配体的化合物一直是加州大学旧金山分校药物的核心方面 设计方面的努力。这套程序有广泛的应用 酶系统，核酸，以及，一般说来，涉及 分子识别。当前版本的程序使用琥珀 评估所提出的结合的分子间势函数 几何图形。开发DOCK是为了提出新的先导化合物。它 在各种各样的系统中成功地实现了这一目标， 包括最近未发表的工作，确定了新的抑制剂 HIV逆转录酶。在以下方面也取得了进展： 软件方面。血管紧张素转换酶抑制剂的组合库设计 组织蛋白D与加州大学伯克利分校Ellman实验室合作 已经发布，图形用户界面的第一步是 已经做好了准备。

The Kuntz group activities primariliy involve structure-based ligand design methods. We are interested in extracting structural information with advanced algorithms; computer graphics routines to display structures; refinement procedures; interactive energy minimization with state-of-the-art potential functions; drug design tools such as DOCK and COMBIDOCK. We have begun a program to couple organic synthesis (DIVERSIFY) with computational searching. DIVERSIFY, uses organic transformations to generate a large family of products from specified starting points. The reagents and/or resulting compounds can then be screening using our DOCK technology. The DOCK software package for searching data bases of organic compounds for putative ligands has been a central aspect of UCSF drug design efforts. This suite of programs has wide-ranging applications to enzyme systems, nucleic acids, and, in general, problems involving molecular recognition.The curren version of the program uses the AMBER intermolecular potential functions to evaluate proposed binding geometries. DOCK was developed to propose novel lead compounds. It has been successful in this goal in a wide variety of systems, including recent, unpublished work identifying novel inhibitors of the HIV reverse transcriptase. Progress has also been made on the software front. Combinatorial library design for inhibitors of cathepsin D in collaboration with the Ellman laboratory at UC Berkeley has been published and a first step at a graphical user interface has been prepared.