title: Molecular crowding effects on conformation and stability of G-quadruplex DNA structure: insights from molecular dynamics simulation.
abstract: 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.
authors.affiliation: Biophysical Chemistry Laboratory, Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran. Electronic address: as.verdian@stu.um.ac.ir.
authors.forename: A
authors.initials: A
authors.lastname: Verdian Doghaei
authors.affiliation: Biophysical Chemistry Laboratory, Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
authors.forename: M R
authors.initials: MR
authors.lastname: Housaindokht
authors.affiliation: Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, Iran.
authors.forename: M R
authors.initials: MR
authors.lastname: Bozorgmehr
mesh_terms: D018360:Crystallography, X-Ray; D000431:Ethanol / Q000737:chemistry; D054856:G-Quadruplexes; D006801:Humans; D006860:Hydrogen Bonding; D046911:Macromolecular Substances / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation
chemical_list: D046911:Macromolecular Substances; D000431:Ethanol
keywords: Cosolute; Ethanol; Gromacs; Hoogsteen hydrogen bond