Sequence-dependent genesis of similar collective states in DNA molecules under low external torque

Molecular biology and biophysics use mathematical modelling to understand how DNA bends and responds to weak torque. The aim of this work is to test the influence of short nucleotide mutations on DNA flexibility using the APOE and COL4A1 genes as examples. In this study, we used an angular mechanical DNA model to investigate the dynamics of collective conformational changes in the APOE and COL4A1 genes under external torque. It was found that even weak torsional stress leads to the formation of regions with similar collective states and bends. The calculations revealed a clear dependence of the formation of these states on both the magnitude of the external stress and the nucleotide sequence. The zones of bends and conformational transitions are located in different regions of the sequence for different genes, which directly confirms the dependence of DNA rigidity on its nucleotide composition. The studied genes are of key physiological importance. The APOE gene regulates lipid metabolism and neuronal function. Its polymorphisms determine individual risk for developing neurodegenerative and cardiovascular diseases. The COL4A1 gene encodes a major protein of basement membranes. Its hereditary defects cause systemic vascular pathologies affecting the brain, kidneys, and organs of vision, demonstrating the critical role of the vascular basement membrane for the stability of these organs. The obtained calculation results open a path to understanding how the primary structure of DNA influences the topology of the molecule, which, in turn, could clarify the mechanisms linking topological changes in DNA to the emergence of mutational trajectories.