PERTURBING FORCES TO HIV 1 PROTEASE STRUCTURE: STRUCTURE BASED DRUG DESIGN

针对HIV-1蛋白酶的基于结构的药物设计工作 抑制作用已经产生了几十种可在化学上获得X射线晶体 结构. 该集合包括耐药性突变体、多个 晶体形式和配体的变化。 的相对重要性 这些因素通过结构性差异表达出来， 探讨了 我们特别关切的是， 与每个变量相关的方差以及 差异是显而易见的。 这些结构的相对重要性 细节对于合理的药物设计和 对耐药突变蛋白酶的结构研究进行解释。

Structure based drug design efforts aimed at HIV-1 protease inhibition have produced dozens of publically available X-ray crystal structures. This ensemble includes drug resistance mutants, multiple crystal forms, and variation in ligand. The relative importance of these factors, as expressed through structural variance, is being explored. Particularly, we are concerned with the magnitude of variance associated with each variable as well as where the differences are manifest. The relative importance of these structural details are of consequence for rational drug design and for interpreting structural studies on drug resistant mutant proteases.