Department of Physics of Complex Systems, S. N. Bose National Centre for Basic Sciences, Block-JD, Sector-III, Salt Lake, Kolkata 700106, India.
Department of Physics of Complex Systems, S. N. Bose National Centre for Basic Sciences, Block-JD, Sector-III, Salt Lake, Kolkata 700106, India.
Biophys Chem. 2023 Oct;301:107079. doi: 10.1016/j.bpc.2023.107079. Epub 2023 Jul 25.
Several experimental studies have shown that Hoogsteen (HG) base pair (bp) stabilizes in the presence of proteins. The molecular mechanism underlying this stabilization is not well known. This leads us to examine the stability of the HG bp in duplex DNA using all-atom molecular dynamics simulation in both the absence and presence of proteins. We use conformational thermodynamics to investigate the stability of a HG bp in duplex DNA at the molecular level. We compute the changes in the conformational free energy and entropy of DNA when DNA adopts a HG bp in its bp sequence rather than a Watson-Crick (WC) bp in both naked DNA and protein-bound DNA complex. We observe that the presence of proteins stabilizes and organizes the HG bp and the entire DNA duplex. Sugar-phosphate, sugar-base, and sugar-pucker torsion angles play key roles in stabilizing and ordering the HG bp in the protein-bound DNA complex.
几项实验研究表明，Hoogsteen（HG）碱基对（bp）在蛋白质存在的情况下会稳定。这种稳定的分子机制尚不清楚。这促使我们使用全原子分子动力学模拟在没有蛋白质和有蛋白质存在的情况下检查双链 DNA 中 HG bp 的稳定性。我们使用构象热力学在分子水平上研究双链 DNA 中 HG bp 的稳定性。我们计算了当 DNA 在其碱基序列中采用 HG bp 而不是 Watson-Crick（WC）bp 时，DNA 的构象自由能和熵的变化，无论是在裸露的 DNA 还是在与蛋白质结合的 DNA 复合物中。我们观察到蛋白质的存在稳定并组织 HG bp 和整个 DNA 双链。糖-磷酸、糖-碱基和糖-环扭转角在稳定和有序排列蛋白质结合的 DNA 复合物中的 HG bp 中起着关键作用。
