School of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi, India.
Computational Science Division, Saha Institute of Nuclear Physics, Kolkata, West Bengal, India.
J Biomol Struct Dyn. 2022;40(21):11373-11382. doi: 10.1080/07391102.2021.1960193. Epub 2021 Aug 6.
Denaturation of the DNA double helix inside the cell is essential for cellular processes such as replication and transcription for the growth of the cells. However, the growth of unwanted cells, which are responsible for cancerous kind of disease, is one of the biggest challenges of modern therapeutics. DNA cross-linking agents may kill cancer cells by damaging their DNA and stopping them from dividing. In the present study, we have carried out steered molecular dynamics simulations to study the effects of rupture and unzipping forces on the stability of dsDNA in the absence and presence of covalently bonded drugs. We have found that the stability of dsDNA increases strongly in the presence of covalently bonded drugs. The microscopic study of disruption of hydrogen-bonds associated with base-pairs of the dsDNA and the study of the variation of stacking overlap parameters gives evidence of symmetry during the rupture and asymmetry in the unzip event. The significance of the mechanism of force-induced melting study of the dsDNA in the absence and presence of antitumor drugs might have a biological relevance as it provides a pathway to open the double helix in a specific position and may help for the pharmaceutical design of drugs.Communicated by Ramaswamy H. Sarma.
细胞内 DNA 双螺旋的变性对于细胞的生长是必不可少的，例如复制和转录等过程。然而，不受控制的细胞生长是现代治疗的最大挑战之一，这些不受控制的细胞是导致癌症等疾病的原因。DNA 交联剂可以通过破坏癌细胞的 DNA 并阻止其分裂来杀死癌细胞。在本研究中，我们进行了定向分子动力学模拟，以研究在不存在和存在共价键合药物的情况下，断裂和拉开力对 dsDNA 稳定性的影响。我们发现，在存在共价键合药物的情况下，dsDNA 的稳定性大大增强。dsDNA 中氢键与碱基对相关联的破坏的微观研究以及堆积重叠参数变化的研究为断裂过程中的对称性和拉开过程中的非对称性提供了证据。研究无抗肿瘤药物和有抗肿瘤药物存在下 dsDNA 的力诱导熔融机制的意义可能具有生物学相关性，因为它为在特定位置打开双链提供了一种途径，并且可能有助于药物的药物设计。由 Ramaswamy H. Sarma 传达。
