Molecular crowding effects on conformation and stability of G-quadruplex DNA structure: insights from molecular dynamics simulation.

Intracellular space is highly crowded with different biomolecules such as proteins, nucleic acids and ions. Therefore molecular crowding is a crucial factor in determining the structure, stability and function of G-quadruplexs. The effect of crowding on the DNA G-quadruplexes structure and stability has been studied by experimental methods, but it hasn't been known how crowding agents stabilize the G-quadruplex structure in molecular level yet. Here, we present a molecular dynamics investigation over the effect of molecular crowding, imitated here by ethanol, on the stability of G-quadruplex structure both in presence and absence of stabilizing K(+) cations. It was demonstrated that G-quadruplex structure in the water collapses in the absence of this cation, while ethanol stabilizes the structure of G-quadruplex by the excluded volume and decreases the water activity. The presence of ethanol can increase the stability of the Hoogsteen hydrogen bonds within the G-quartet. To understand the importance of cations, simulation has been performed on the cation containing G-quadruplex in the presence of ethanol with different concentrations. Molecular dynamics simulations of the structure and stability of human telomeric G-quadruplex in ethanol containing solution has enhanced our understanding on how the parallel-stranded G-quadruplex is affected in a condition where the water content is reduced.