Understanding the self-assembly dynamics of A/T absent 'four-way DNA junctions with sticky ends' at altered physiological conditions through molecular dynamics simulations

Elucidation of structure and dynamics of alternative higher-order structures of DNA such as in branched form could be targeted for therapeutics designing. Herein, we are reporting the intrinsically dynamic and folds transitions of an unusual DNA junction with sequence d(CGGCGGCCGC)(4) which self-assembles into a four-way DNA junction form with sticky ends using long interval molecular simulations under various artificial physiological conditions. The original crystal structure coordinates (PDB ID: 3Q5C) for the selected DNA junction was considered for a total of 1.1 mu s molecular dynamics simulation interval, including different temperature and pH, under OPLS-2005 force field using DESMOND suite. Following, post-dynamics structure parameters for the DNA junction were calculated and analyzed by comparison to the crystal structure. We show here that the self-assembly dynamics of DNA junction is mitigated by the temperature and pH sensitivities, and discloses peculiar structural properties as function of time. From this study it can be concluded on account of temperature sensitive and pH dependent behaviours, DNA junction periodic arrangements can willingly be synthesized and redeveloped for multiple uses like genetic biomarkers, DNA biosensor, DNA nanotechnology, DNA Zipper, etc. Furthermore, the pH dis-regulation behaviour may be used to trigger the functionality of DNA made drug-releasing nanomachines.

Automated summary

In this study, we investigated the dynamic folding transitions of a unique DNA junction and its self-assembly into a four-way DNA junction form with sticky ends. Molecular dynamics simulations were conducted under various physiological conditions, and the post-dynamics structure parameters were compared with the crystal structure. It was found that the self-assembly dynamics of the DNA junction were temperature and pH sensitive, revealing peculiar structural properties over time. These findings have implications for the synthesis and development of DNA junctions for various applications, such as genetic biomarkers and drug-releasing nanomachines triggered by pH dis-regulation.