Mathur Neha, Singh Amar, Singh Navin
Department of Physics, Birla Institute of Technology & Science, Pilani 333031, India.
Center for Computational Biology, The University of Kansas, Lawrence, KS 66047, USA.
Int J Mol Sci. 2025 May 31;26(11):5305. doi: 10.3390/ijms26115305.
Recent advances in molecular dynamics (MD) simulations and the introduction of artificial intelligence (AI) have resulted in a significant increase in accuracy for structure prediction. However, the cell is a highly crowded environment consisting of various macromolecules, such as proteins and nucleic acids. The macromolecular crowding and solution conditions, such as temperature, ion concentration, and the presence of crowders, significantly influence the molecular interactions between and structural changes in proteins and nucleic acids. In this study, we investigate the presence of crowders and their effect on the melting of DNA molecules by analyzing melting profiles of short and long heterogeneous DNA duplexes. In particular, we examine how multiple inert crowders, randomly distributed along long DNA chains, influence DNA melting. We find that the presence of crowders stabilizes double-stranded DNA (dsDNA), with this effect being more pronounced in short DNA duplexes. These findings complement in vitro observations and improve our understanding of dsDNA in cell-like environments.
分子动力学（MD）模拟的最新进展以及人工智能（AI）的引入，使得结构预测的准确性显著提高。然而，细胞是一个由各种大分子（如蛋白质和核酸）组成的高度拥挤的环境。大分子拥挤以及诸如温度、离子浓度和拥挤剂的存在等溶液条件，会显著影响蛋白质和核酸之间的分子相互作用以及结构变化。在本研究中，我们通过分析短的和长的异质DNA双链体的解链曲线，研究拥挤剂的存在及其对DNA分子解链的影响。特别是，我们研究了沿着长DNA链随机分布的多个惰性拥挤剂如何影响DNA解链。我们发现拥挤剂的存在会使双链DNA（dsDNA）稳定，这种效应在短DNA双链体中更为明显。这些发现补充了体外观察结果，并增进了我们对类细胞环境中dsDNA的理解。
