Melting and Bubble Formation in a Double-Stranded DNA: Microscopic Aspects of Early Base-Pair Opening Events and the Role of Water

Mondal, S and Mukherjee, S and Bagchi, B (2024) Melting and Bubble Formation in a Double-Stranded DNA: Microscopic Aspects of Early Base-Pair Opening Events and the Role of Water. In: Journal of Physical Chemistry B, 128 (9). pp. 2076-2086.

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Abstract

Despite its rigid structure, DNA is a remarkably flexible molecule. Flexibility is essential for biological functions (such as transcription and gene repair), which require large-amplitude structural changes such as bubble formation. The bubbles thus formed are required to have a certain stability of their own and survive long on the time scale of molecular motions. A molecular understanding of fluctuations leading to quasi-stable structures is not available. Through extensive atomistic molecular dynamics simulations, we identify a sequence of microscopic events that culminate in local bubble formation, which is initiated by base-pair (BP) opening, resulting from the cleavage of native BP hydrogen bonds (HBs). This is followed by the formation of mismatched BPs with non-native contacts. These metastable structures can either revert to their original forms or undergo a flipping transition to form a local bubble that can span across 3-4 BPs. A substantial distortion of the DNA backbone and a disruption of BP stacking are observed because of the structural changes induced by these local perturbations. We also explored how water helps in the entire process. A small number of water molecules undergo rearrangement to stabilize the intermediate states by forming HBs with DNA bases. Water thus acts as a lubricant that counteracts the enthalpic penalty suffered from the loss of native BP contacts. Although the process of bubble formation is reversible, the sequence of steps involved poses an entropic barrier, preventing it from easily retracing the path to the native state. © 2024 American Chemical Society

Item Type:	Journal Article
Publication:	Journal of Physical Chemistry B
Publisher:	American Chemical Society
Additional Information:	The copyright for this article belongs to American Chemical Society.
Keywords:	Bubble formation; Hydrogen bonds; Molecular dynamics; Transcription, Base pairs; Biological functions; Flexible molecules; Gene repairs; Large amplitude; Molecular motions; Molecular understanding; Role of water; Stable structures; Time-scales, DNA, DNA; water, base pairing; chemistry; conformation; molecular dynamics, Base Pairing; DNA; Molecular Dynamics Simulation; Nucleic Acid Conformation; Water
Department/Centre:	Division of Chemical Sciences > Solid State & Structural Chemistry Unit
Date Deposited:	16 May 2024 05:46
Last Modified:	16 May 2024 05:46
URI:	https://eprints.iisc.ac.in/id/eprint/84520

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