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 (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.