关于DNA发夹d(GCGAAGC)与芳香族药物络合时稳定性降低的起源

On the origin of the decrease in stability of the DNA hairpin d(GCGAAGC) on complexation with aromatic drugs.

作者信息

Kostjukov V V, Lantushenko A O, Davies D B, Evstigneev M P

机构信息

Department of Physics, Sevastopol National Technical University, Studgorodok, Sevastopol, 99053, Crimea, Ukraine.

出版信息

Biophys Chem. 2007 Aug;129(1):56-9. doi: 10.1016/j.bpc.2007.05.005. Epub 2007 May 18.

DOI:10.1016/j.bpc.2007.05.005

PMID:17544564

Abstract

Molecular dynamics simulations of drug-DNA complexes have been carried out in order to explain the experimentally observed decrease in thermal stability of the DNA hairpin d(GCGAAGC) on binding the aromatic drug molecules, daunomycin, ethidium bromide, novantrone and proflavine. This complexation behavior is in contrast to the stabilizing effect of the same aromatic drug molecules on DNA duplexes. Analysis of the energy parameters and the hydration properties of the complexes shows that the main factor correlating with the decrease in melting temperatures of the drug-hairpin complexes is the number of water bridges, with a reduction of at least 40% on ligand binding.

摘要

为了解释实验观察到的DNA发夹d(GCGAAGC)与芳香族药物分子柔红霉素、溴化乙锭、诺凡沙星和原黄素结合后热稳定性下降的现象，已对药物-DNA复合物进行了分子动力学模拟。这种络合行为与相同芳香族药物分子对DNA双链体的稳定作用形成对比。对复合物的能量参数和水合性质的分析表明，与药物-发夹复合物解链温度降低相关的主要因素是水桥的数量，配体结合后水桥数量至少减少40%。