Fanelli F, Menziani M C, De Benedetti P G
Dipartimento di Chimica, Università di Modena, Italy.
Bioorg Med Chem. 1995 Nov;3(11):1465-77. doi: 10.1016/0968-0896(95)00131-y.
Molecular dynamics simulations of the rat m3-muscarinic seven-helix-bundle receptor models were performed on the free, agonist-bound and antagonist-bound forms. A comparative structural/dynamics analysis was performed in order to explain the perturbations induced by the functionally different ligands when binding to their target receptor. Theoretical quantitative structure-activity relationship models were developed; a good correlation was obtained between the interaction energies of the minimized average ligand-receptor complexes and the pharmacological affinities of the considered ligands. The consistency obtained between the structural rearrangement of the transmembrane seven-helix-bundle models considered and the experimental pharmacological efficacies and affinities of the ligands constitutes an important validation of the 3-D models proposed and allows the inference of the mechanism of ligand-induced or mutation-induced receptor activation at the molecular level.
对大鼠M3型毒蕈碱七螺旋束受体模型的游离形式、激动剂结合形式和拮抗剂结合形式进行了分子动力学模拟。进行了比较结构/动力学分析，以解释功能不同的配体与靶受体结合时引起的扰动。建立了理论定量构效关系模型；在最小化的平均配体-受体复合物的相互作用能与所考虑配体的药理亲和力之间获得了良好的相关性。所考虑的跨膜七螺旋束模型的结构重排与配体的实验药理效力和亲和力之间获得的一致性，构成了对所提出的三维模型的重要验证，并允许在分子水平上推断配体诱导或突变诱导的受体激活机制。
