α7-nAChR和α9α10-nAChR的同源模建研究

Homology modeling of α7-nAChR and α9α10-nAChR

目的:构建了人的α7-nAChR和α9α10-nAChR的二聚体模型。方法:采用同源模建和分子动力学的方法,以高同源性的2QC1和2BYR作为复合模板,构建了人的α7-nAChR和α9α10-nAChR的二聚体模型,并通过PROCHECK、ERRAT及PROSA程序对其进行了构象和能量的评价。结果:通过对200 ps,500 ps,1.2 ns下模型的C-loop区进行比较分析发现:1.2 ns下模型的C-1oop区构象更趋于合理状态。对所建模型进行构象和能量的评价以及分子对接的验证结果表明:本文中模建的α7-nAChR和α9α10-nAChR模型是合理的、可靠的。结论:该研究所建立的模型是合理可靠的,为设计α7-nAChR和α9α10-nAChR的高选择性配体提供了重要的理论基础。

Objective： To construct human α7-nAChR and α9α10-nAChR dimer models. Methods： In this paper, the human u7-nAChR and α9α10-nAChR dimer models were constructed respectively using homology modeling and MD simulation with the multi-templates consisting of 2QC 1 and 2BYR, and then were assessed with stereochemical and energetic aspects by PROCHECK, ERRAT and PROSA program. Results It could be determined that the conformations of two models in 1.2 ns are the most reasonable state compared with others in 200 ps and 500 ps. The stereochemical, energetic evaluation and docking results confirm the rationality and reliability of human α7-nAChR and α9α10-nAChR dimer models we built. Conclusion： The models we established in this paper are feasible and reasonable. The current results might provide the theoretical guidance for future rational design of subtype-selective ligands.