Department of Chemistry "G. Ciamician", University of Bologna, Bologna, Italy.
Curr Med Chem. 2012;19(11):1587-601. doi: 10.2174/092986712799945030.
In the last years, molecular docking emerged as a powerful tool to investigate the interactions between opioid ligands and their receptors, thus driving the design and development of new selective agonists or antagonists of therapeutic interest. This review especially covers the most representative and recent comparative molecular docking analyses of structurally related compounds, as well as of agonists and antagonists within the active and inactive states of the receptors. The comparative analyses gave important information on the structural determinants responsible for the affinity and selectivity of the ligands, and defined the features responsible for the activation of the receptors. A special section is dedicated to the analyses of recently discovered, unusual agonists lacking of the tyramine pharmacophore, such as Salvinorin A, and the cyclopeptides which comprise the D-Trp-Phe pharmacophoric motif. For the atypical structure of these compounds, the docking proved to be essential to disclose how they interact with and activate the receptors.
在过去的几年中，分子对接技术已成为研究阿片类配体与其受体相互作用的有力工具，从而推动了具有治疗意义的新型选择性激动剂或拮抗剂的设计和开发。本综述特别涵盖了对结构相关化合物以及受体的活性和非活性状态下的激动剂和拮抗剂的最具代表性和最新的比较分子对接分析。这些比较分析提供了有关配体亲和力和选择性的结构决定因素的重要信息，并确定了负责受体激活的特征。专门有一部分用于分析最近发现的缺乏酪胺药效团的不寻常激动剂，如 Salvinorin A，以及包含 D-Trp-Phe 药效团的环肽。对于这些化合物的非典型结构，对接证明对于揭示它们如何与受体相互作用并激活受体至关重要。
