Molecular Crowder-Induced Structural Transformation of the DNA Dodecamer

Molecular crowding plays a crucial role in shaping the
structural
landscape of biomolecules, influencing their stability, interactions,
and functional behavior. In vivo, these crowders include biomolecules
such as proteins, nucleic acids, and metabolites within the crowded
cellular environment, whereas in vitro, they are represented by various
organic and inorganic molecules. Understanding how these crowders
affect DNA conformation is essential for elucidating their impact
on genetic processes. In this study, we explore how molecular crowders
influence the structural transformations of a DNA dodecamer sequence
using atomistic molecular dynamics simulations. Specifically, we examine
the effects of aspartame and polyethylene glycol (PEG-200) as crowding
agents. Our findings reveal distinct interaction patterns: while PEG-200
molecules preferentially accumulate near the termini of the DNA, aspartame
molecules exhibit a strong affinity for DNA grooves, leading to structural
stabilization at lower concentrations and clustering-induced perturbations
at higher concentrations. Further, by analyzing key structural descriptors,
we elucidate the influence of molecular crowding on DNA organization.
These insights contribute to a deeper understanding of how different
crowders modulate DNA structure in crowded environments, offering
broader implications for biomolecular organization in physiological
and biomimetic systems.