Computational Molecular Biophysics Laboratory, School of Chemical & Biotechnology, SASTRA Deemed to be University, Tirumalaisamudram, Thanjavur, 613401, Tamil Nadu, India.
Computational Molecular Biophysics Laboratory, School of Chemical & Biotechnology, SASTRA Deemed to be University, Tirumalaisamudram, Thanjavur, 613401, Tamil Nadu, India.
J Mol Graph Model. 2022 Jul;114:108169. doi: 10.1016/j.jmgm.2022.108169. Epub 2022 Mar 29.
Osmolytes are a class of organic solutes that are produced in a variety of organisms in response to stress. They exert diverse effects on macromolecules and their functions. In this work, we investigate the effect of glycerol, one such osmolyte, on the hydration and conformation of four DNA sequences that differ by a single base pair and a random DNA sequence. Molecular dynamics simulations reveal DNA sequence-dependent and glycerol concentration-dependent hydration and DNA conformation. Interestingly, we find that the sequence-dependent changes in the hydration reflects the order of preference of these sequences for star activity of the EcoRI enzyme. However, the changes in DNA conformation do not reflect this order of preference. Interaction energy analyses reveal that the per-glycerol interaction energy with DNA is stronger than the per-water interaction energy with DNA. However, the total interaction energy of glycerol with DNA is lower than that of total water-DNA interaction energy indicating that it might be easier for an approaching DNA-binding protein to displace glycerol than water and thus contributing positively to protein-DNA binding. In a larger context, our study brings attention to the need to investigate the effect of osmolytes on free DNA in order to delineate the role of osmolyte in protein-DNA interactions.
渗透物是一类有机溶质，在各种生物体中都会产生，以应对压力。它们对大分子及其功能产生多种影响。在这项工作中，我们研究了甘油（一种渗透物）对四个碱基对和一个随机 DNA 序列不同的 DNA 序列的水合和构象的影响。分子动力学模拟揭示了 DNA 序列依赖性和甘油浓度依赖性的水合作用和 DNA 构象。有趣的是，我们发现水合作用的序列依赖性变化反映了这些序列对 EcoRI 酶的星活性的偏好顺序。然而，DNA 构象的变化并不反映这种偏好顺序。相互作用能分析表明，甘油与 DNA 的每克相互作用能大于水与 DNA 的每克相互作用能。然而，甘油与 DNA 的总相互作用能低于总水-DNA 相互作用能，这表明接近的 DNA 结合蛋白置换甘油比置换水更容易，从而对蛋白质-DNA 结合产生积极影响。从更大的角度来看，我们的研究引起了人们的注意，需要研究渗透物对游离 DNA 的影响，以阐明渗透物在蛋白质-DNA 相互作用中的作用。
