Large system/ low cost methods for bond breaking

Questions
#1

I am currently studying DNA systems to understand how chromosomal translocation is triggered and carried out in eukaryotic systems. This requires I study very large systems (~750 atoms, ~8000 basis functions).

The focus of the work is on the breaking of two bonds connecting two residues in a DNA oligomer which are also subject to the presence of other residues in the adjacent areas of the DNA double helix. So, dispersion, charge-charge interactions and other quantum effects - especially strong correlation of the bonds being broken, need to be included in the analysis.

I looked through the Q-Chem manual for how to do this analysis. Unfortunately, I was not able to decide what methods/ models would be best to do this study.

Anyone have any suggestions on how this can be done with a method that will yield meaningful results?

Any suggestions would be appreciated.

#2

For a system that large, you are limited to DFT or semi-empirical methods. Of the latter, there are only a few in Q-Chem and none of them were designed for bond breaking so I’d be wary. That means something like wB97X-D/6-31G* may be your best bet.

#3

Thank you for your reply. Would an Unrestricted wB97X-D/def2-SVP make sense?

#4

Yes, should definitely be unrestricted (I forgot to mention). For speed in a large system, you might even try def2-SV(P), which omits polarization functions on hydrogen.