Ali Asfa, Bansal Manju, Bhattacharya Santanu
Department of Organic Chemistry, Indian Institute of Science , Bangalore 560 012, India.
J Phys Chem B. 2015 Jan 8;119(1):5-14. doi: 10.1021/jp505792z. Epub 2014 Dec 19.
The binding of ligand 5,10,15,20-tetra(N-methyl-4-pyridyl)porphine (TMPyP4) with telomeric and genomic G-quadruplex DNA has been extensively studied. However, a comparative study of interactions of TMPyP4 with different conformations of human telomeric G-quadruplex DNA, namely, parallel propeller-type (PP), antiparallel basket-type (AB), and mixed hybrid-type (MH) G-quadruplex DNA, has not been done. We considered all the possible binding sites in each of the G-quadruplex DNA structures and docked TMPyP4 to each one of them. The resultant most potent sites for binding were analyzed from the mean binding free energy of the complexes. Molecular dynamics simulations were then carried out, and analysis of the binding free energy of the TMPyP4-G-quadruplex complex showed that the binding of TMPyP4 with parallel propeller-type G-quadruplex DNA is preferred over the other two G-quadruplex DNA conformations. The results obtained from the change in solvent excluded surface area (SESA) and solvent accessible surface area (SASA) also support the more pronounced binding of the ligand with the parallel propeller-type G-quadruplex DNA.
配体5,10,15,20-四（N-甲基-4-吡啶基）卟啉（TMPyP4）与端粒和基因组G-四链体DNA的结合已得到广泛研究。然而，尚未对TMPyP4与人类端粒G-四链体DNA不同构象（即平行螺旋桨型（PP）、反平行篮型（AB）和混合杂合型（MH）G-四链体DNA）的相互作用进行比较研究。我们考虑了每个G-四链体DNA结构中的所有可能结合位点，并将TMPyP4对接至其中的每一个位点。根据复合物的平均结合自由能分析得到的最有效结合位点。随后进行了分子动力学模拟，对TMPyP4-G-四链体复合物结合自由能的分析表明，TMPyP4与平行螺旋桨型G-四链体DNA的结合优于其他两种G-四链体DNA构象。从溶剂排除表面积（SESA）和溶剂可及表面积（SASA）变化获得的结果也支持配体与平行螺旋桨型G-四链体DNA的结合更为显著。
