端粒G-四链体结合酞菁分子的分子模拟研究

Molecular Simulation Study of the Binding Interaction between Telomere G-quadruplex and Phthalocyanine Molecule

为揭示负电性稳定剂与人端粒G-四链体的作用机制,采用分子对接和分子动力学方法对新型负电性四磺酸酞菁分子(anionic phthalocyanine 3,4′,4″,4^(■)-tetrasulfonic acid)和人端粒平行构象G-四链体进行了系统研究。构象分析发现,酞菁分子能够单独或同时稳定结合于G-四链体的顶层和底层G-四分体平面并有效提高G-四链体的稳定性;结合自由能分析表明,酞菁分子堆叠于顶层G-四分体的结合模式在能量上更为有利,同时第二个酞菁分子的引入能够进一步提升结合强度。这些发现对新型端粒G-四链体稳定剂的开发具有重要的指导意义。

In order to reveal the mechanism of interaction between the negatively charged stabilizer and the human telomere G-quadruplex,the current work applies molecular docking and molecular dynamics methods to the novel anionic phthalocyanine molecule(anionic phthalocyanine 3,4′,4″,4^(■)-tetrasulfonic acid)and human telomere parallel G-quadruplex.Conformational analysis finds that the phthalocyanine molecule bind stably to the top and bottom G-tetrads of the G-quadruplex alone or at the same time,which effectively improve the stability of the G-quadruplex;binding free energy analysis shows that the top G-tetrad stacking binding mode of the phthalocyanine molecule is energetically more favorable,and the introduction of the second phthalocyanine molecule would further enhance the binding strength.These findings have important guiding significance for the development of novel telomere G-quadruplex stabilizers.