All-Atom MD Simulation of DNA Condensation Using Ab Initio Derived Force Field Parameters of Cobalt(III)-Hexammine.

It is well established that the presence of the trivalent cobalt(III)-hexammine cation (CoHex) 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 CoHex has previously not been demonstrated. In order to obtain a rigorous description of CoHex-nucleic acid interactions and CoHex-induced DNA condensation to be used in MD simulations, we have derived optimized force field parameters of the CoHex ion. They were obtained from Car-Parrinello molecular dynamics simulation of a single CoHex 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 CoHex. 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 CoHex interaction with DNA. A control simulation with a similar setup but in the presence of Mg does not induce DNA-DNA attraction, which is also in agreement with experiment.