My ligand is a small gold nanocluster built from a unit cell. Thus it must be rigid. I added needed constants for gold to the parameter file in the autodock and put the number of active torsions to be zero. Final binding energy is positive due to the high positive value of torsional free energy while interaction energy is negative.
Uttam Pal I did not open it as rigid. Just opened ligand, then set active torsions to zero and saved the pdbqt. Receiptor is rigid.
Andrii Lesiuk I checked and somehow setting number of torsions (Ntor) is not enough. Maybe a bug in the code. As described in here (http://autodock.scripps.edu/resources/science/equations/) the torsional free energy is calculate by the following equation:
ΔGtor = Wtor Ntor
If you set the empirical coefficient Wtor to zero by changing the value in the following line in AD4 parameter file (http://autodock.scripps.edu/faqs-help/faq/where-do-i-set-the-autodock-4-force-field-parameters):
form
FE_coeff_tors 0.2744
to
FE_coeff_tors 0.0
It will work.
Uttam Pal I got what you meant. Set ligand as rigid, and consequently torsdof=0 in pdbqt (which is N_tor). But somehow final glg-file still contains non-zero torsional energy while torsdof is zero).
The other option is to simply ignore torsional energy and take interaction energy term as binding energy, isn't it? I think N_tor does not affect intermolecular energy.
Great. Thanks a lot, Uttam Pal, for the conversation. It helps to get rid of doubts.
By the way, the number of torsions is a quite subtle issue. Found accidentally the following article Article Effect of ligand torsion number on the AutoDock mediated pre...
Andrii Lesiuk Thanks for starting this discussion. Torsion over rotatable bonds is directly related to the entropy of the molecule. A ligand with many rotatable bonds has large conformational entropy. So, ΔGtor is basically the entropy term in the forcefield as discussed in the original article on the semiempirical forcefield used in AutoDock (https://onlinelibrary.wiley.com/doi/full/10.1002/jcc.20634). In a gold cluster, the Au-Au bonds are not actually rotatable. The bonds got misassigned as rotatable so, this term can be ignored.
Sriramulu et al. argued in their article that the underestimation of binding energies they found in some lignads was due to the large penalty imposed by the conformational entropy of the ligands and, therefore, they tried to recalculate the coefficient. However, I am not confident about their method and the results they got as simply setting the number of torsions to a lower value does not actually change the calculated ΔGtor , although it can result in a change in the total binding energy value. In the entropy calculations, all the rotatable bonds (irrespective of whether set free or not) are taken into account (not a bug in the code as I thought in my earlier comment).
- Badges
- Science topic
- Similar topics
- Biological Science
- Biochemistry
- Enzymology
- Enzymes