Comment on Molecular Dynamics Simulations of Zinc Ions in Water Using CHARMM"

Obst, Stefan; Stote, Roland H.

doi:10.1007/s008940050077

Cited by 2 publications

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…34–36 The validation of these two divalent metal ions is particularly important given that divalent ion MD simulations have been shown less reliable than simulations of monovalent ions. 40–42 The other ions investigated here have not yet been experimentally validated with FdU; however, they have been applied in a variety of other studies of nucleic acids in the presence of various ions of which we cite a few examples. 43–45 Obviously, the results for these ions are only as valid as the input forcefield parameters.…”

Section: Methodsmentioning

confidence: 99%

All-atom MD indicates ion-dependent behavior of therapeutic DNA polymer

Melvin

Gmeiner

Salsbury

2017

Phys. Chem. Chem. Phys.

View full text Add to dashboard Cite

Understanding the efficacy of and creating delivery mechanisms for therapeutic nucleic acids requires understanding structural and kinetic properties which allow these polymers to promote the death of cancerous cells. One molecule of interest is a 10mer of FdUMP (5-fluoro-2′-deoxyuridine-5′-O-monophosphate) – also called F10. Here we investigate the structural and kinetic behavior of F10 in intracellular and extracellular solvent conditions along with non-biological conditions that may be efficacious in in vitro preparations of F10 delivery systems. From our all-atom Molecular Dynamics simulations totaling 80 microseconds, we predict that F10’s phosphate groups form close-range interactions with calcium and zinc ions, with calcium having the highest affinity of the five ions investigated. We also predict that F10’s interactions with magnesium, potassium and sodium are almost exclusively long-range interactions. In terms of intramolecular interactions, we find that F10 is least structured (in terms of hydrogen bonds among bases) in the 150mM NaCl (extracellular-like solvent conditions) and most structured in 150mM ZnCl2. Kinetically, we see that F10 is unstable in the presence of magnesium, sodium or potassium, finding stable kinetic traps in the presence of calcium or zinc.

show abstract