Parameters for RNA-ligand docking

HADDOCK
1

I would like to study the binding of different aptamers (RNA sequences) to the ligand PFOA. Haddock allows me to do so, but I don’t know how to tune the parameters to optimize the results, and cannot find any information anywhere. I would really appreciate if someone could give me some notions about how to find the best parameters to perform Haddock in this case. Thanks!

2

Wee never benchmarked RNA-ligand docking but did some yet unpublished work on DNA-ligand modelling. Here is a matrix of parameters (the last column should work for RNA-ligand modelling):

default value Protein/Small molecule Protein/DNA DNA/small molecule
Dieletric constant for it0 dielec_0 rdie cdie rdie cdie
Dieletric constant for it1 dielec_1 rdie cdie rdie cdie
MD steps for rigid body high temperature TAD initiosteps 500 0 500 0
MD steps during first rigid body cooling stage cool1_steps 500 0 500 0
Initial temperature for second TAD cooling step with flexible side-chain at the interface tadinit2_t 1000 500 1000 500
Initial temperature for third TAD cooling step with fully flexible interface tadinit3_t 1000 300 1000 300
Weight of the intermolecular van der Waals energy for scoring at the rigid-body docking stage w_vdw_0 0.01 1 0.01 1
Weight of the intermolecular electrostatic energy for scoring at the final stage w_elec_2 0.2 0.1 0.2 0.1
Dielectric constant for rigid-body docking epsilon_0 10 10 78 78
Dielectric constant for the semi-flexible refinement epsilon_1 10 10 78 10

And in addition you might consider setting the weight of the desolation energy term in the scoring function to 0

3

Thank you so much!