[Dock-fans] Adding charges to a peptide ligand

Sudipto Mukherjee sudmukh at yahoo.com
Thu May 12 15:09:06 PDT 2016

Hi Chris,
DOCK was originally designed with small molecules in mind. While it is possible to dock in small peptides, this is not the normal use case and you might experience mixed results. Pose reproduction success rate drops linearly with the number of rotatable bonds. Docking runtime also increases exponentially with the number of rotatable bonds. A peptide with 21-residues probably has ~80 rotatable bonds, which is unlikely to produce reasonable results. DOCK uses the anchor-and-grow algorithm for flexible docking. This means the conformation of each ligand is "grown" on the fly, torsion by torsion. For a small peptide, you are asking DOCK to perform ab initio protein folding in the binding site. 
If docking in such peptides is critical to your project, I would recommend a different tool focused on protein-protein docking such as RosettaDock.
Rosetta 3.4: Docking Protocol (RosettaDock)
Having said that, I have successfully docked in small peptides (all alpha helices) with DOCK6.7.  If you still want to use DOCK for this project, (e.g. as a baseline to compare with small molecule screens) let me know and I'll provide more details of how this could made to work with restrictions (rigidly dock the backbone and optimize sidechains).  

    On Thursday, May 12, 2016 5:37 PM, Chris Fage <cdfage at gmail.com> wrote:

I am interested on testing the abilities of dock6 on a 21-residue peptide ligand. When I use the Add Charge tool in Chimera, I see the error message below. I am grateful for any suggestions.

Model 0 (peptide.pdb) appears to be a protein without secondary structure assignments.Automatically computing assignments using 'ksdssp' and parameter values:  energy cutoff -0.5  minimum helix length 3  minimum strand length 3Use command 'help ksdssp' for more information.Charge model: AMBER ff12SBAssigning partial charges to residue HIS (net charge +1) with am1-bcc methodRunning ANTECHAMBER command: /home/chris/.local/UCSF-Chimera64-1.8.1/bin/amber12/bin/antechamber -ek qm_theory='AM1', -i /tmp/tmpYJ5zHd/ante.in.mol2 -fi mol2 -o /tmp/tmpYJ5zHd/ante.out.mol2 -fo mol2 -c bcc -nc 1 -j 5 -s 2(HIS) 
(HIS) Running: /home/chris/.local/UCSF-Chimera64-1.8.1/bin/amber12/bin/bondtype -j part -i ANTECHAMBER_BOND_TYPE.AC0 -o ANTECHAMBER_BOND_TYPE.AC -f ac
(HIS) Running: /home/chris/.local/UCSF-Chimera64-1.8.1/bin/amber12/bin/atomtype -i ANTECHAMBER_AC.AC0 -o ANTECHAMBER_AC.AC -p gaff
(HIS) Total number of electrons: 111; net charge: 1
(HIS) INFO: Number of electrons is odd: 111
(HIS)       Please check the total charge (-nc flag) and spin multiplicity (-m flag)
(HIS) Running: /home/chris/.local/UCSF-Chimera64-1.8.1/bin/amber12/bin/sqm -O -i sqm.in -o sqm.out
(HIS) Error: cannot run "/home/chris/.local/UCSF-Chimera64-1.8.1/bin/amber12/bin/sqm -O -i sqm.in -o sqm.out" of bcc() in charge.c properly, exit
Failure running ANTECHAMBER for residue HISCheck reply log for details

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