jp7b03793_si_001.pdf (175.88 kB)
All-Atom MD Simulation of DNA Condensation Using Ab Initio Derived Force Field Parameters of Cobalt(III)-Hexammine
journal contribution
posted on 2017-07-26, 00:00 authored by Tiedong Sun, Alexander Mirzoev, Nikolay Korolev, Alexander P. Lyubartsev, Lars NordenskiöldIt
is well established that the presence of the trivalent cobalt(III)-hexammine
cation (CoHex3+) at submillimolar concentrations leads
to bundling (condensation) of double-stranded DNA molecules, which
is caused by DNA–DNA attraction induced by the multivalent
counterions. However, the detailed mechanism of this process is still
not fully understood. Furthermore, in all-atom molecular dynamics
(MD) simulations, spontaneous aggregation of several DNA oligonucleotides
in the presence of CoHex3+ has previously not been demonstrated.
In order to obtain a rigorous description of CoHex3+–nucleic
acid interactions and CoHex3+-induced DNA condensation
to be used in MD simulations, we have derived optimized force field
parameters of the CoHex3+ ion. They were obtained from
Car–Parrinello molecular dynamics simulation of a single CoHex3+ ion in the presence of 125 water molecules. The new set
of force field parameters reproduces the experimentally known transition
of DNA from B- to A-form, and qualitatively describes changes of DNA
and RNA persistence lengths. We then carried out a 2 μs long
atomistic simulation of four DNA oligomers each consisting of 36 base
pairs in the presence of CoHex3+. We demonstrate that,
in this system, DNA molecules display attractive interactions and
aggregate into bundle-like structures. This behavior depends critically
on the details of the CoHex3+ interaction with DNA. A control
simulation with a similar setup but in the presence of Mg2+ does not induce DNA–DNA attraction, which is also in agreement
with experiment.
History
Usage metrics
Categories
Keywords
DNA oligonucleotidesforce field parameters36 base pairsoptimized force field parameterssubmillimolar concentrationsatomistic simulationAll-Atom MD SimulationDNA Condensationbundle-like structurescontrol simulationDNA molecules displaypresenceDNA condensationRNA persistence lengthsdynamics simulationacid interactionsDNA oligomers125 water moleculesMD simulations2 μCoHexdouble-stranded DNA moleculesAb Initio Derived Force Field Parameters
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC