Abstract
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.