Flexible backbone for protein-RNA docking

HADDOCK
1

I am doing a protein-RNA docking and I need my double stranded RNA to be flexible while keeping the hydrogen bonds between the nucleotides. Haddock only allows me to select nucleotides as fully flexible and not atoms. So how can I go about this without making restraint files and such?

2

Haddock can automatically generate restraints to help maintain the helical structure of the NA. To achive this:

  • In Haddock2.4 (web server), go to Input data tab and select Nucleic acid (DNA and/or RNA) under What kind of molecule are you docking?* for your RNA input molecule;

  • In Haddock3, use the dnarest_on = true parameter in the sampling and refinement modules.

3

I have already done this but the RNA structure that I am submitting has a certain twist to it which I don’t want affecting the docking as I am getting weird results like this. Is there any way to make it more flexible?

4

I am not sure I follow. If you trying to preserve this twist while keeping molecule flexible, then you could try adding several unambigouos restraints to maintain RNA shape.

If it’s the opposite and you don’t want this twist in the outcome - perhaps try generating different input RNA conformation (prior to the docking), e.g. with refinement/short MD (may-be one of the refinement modules of Haddock3 can help, e.g. mdref) or tools like SimRNA.

Finally, if you want to increase docking flexibility in general, you could adapt refinement/it1 parameters, e.g. increase the number of MD steps or the temperature. But please be avare that this will 1. influence all docking partners, 2. increase the use of comutational resuorses and docking time.