trRosetta modelling with a ligand

Hi all,

I am trying to modify the trRosetta scripts to run it with a ligand (heme; I added few distance constraints between the protein residues and atoms in the ligand).

I ran molfile2params with the -c flag and have both centroid and full atom params and pdb files of the ligand. I inserted the ligand to the pose and converted it to centroid mode for the initial folding calculations. When I add my ligand constraints prior to the minimization stage, after all the network constraints are read, I get the following error:

short + medium + long

core.scoring.constraints.ConstraintsIO: read constraints from /dev/shm/iitdrgdh/minimize.cst

core.scoring.constraints.ConstraintsIO: Read in 66646 constraints

core.optimization.Minimizer: [ WARNING ] LBFGS MAX CYCLES 1000 EXCEEDED, BUT FUNC NOT CONVERGED!



ERROR: ResidueType OHE does not have an atom CEN

ERROR:: Exit from: /home/benchmark/rosetta/source/build/PyRosetta/linux/clang-3.4.2/python-3.6/release/source/src/core/chemical/ResidueType.hh line: 426

Traceback (most recent call last):

File "../trRosetta.py", line 232, in <module>

main()

File "../trRosetta.py", line 176, in main

repeat_mover.apply(pose)

RuntimeError:



File: /home/benchmark/rosetta/source/build/PyRosetta/linux/clang-3.4.2/python-3.6/release/source/src/core/chemical/ResidueType.hh:426

[ ERROR ] UtilityExitException

ERROR: ResidueType OHE does not have an atom CEN

The repeat mover comes from the following piece of code in the trRosetta.py script:

mmap = MoveMap()

map.set_bb(True)

map.set_chi(False)

mmap.set_jump(True)

:

min_mover = MinMover(mmap, sf, 'lbfgs_armijo_nonmonotone', 0.0001, True)

min_mover.max_iter(1000)

:

repeat_mover = RepeatMover(min_mover, 3)

The molfile2params script does not add a CEN atom to the ligand (heme), and I did not find example in the database for any ligand’s centroid params file with such an atom (only for amino acids). CEN atom also does not make sense in the case of a heme molecule as it cannot accuretly represent the volume of the flat molecule. Furthermore, I used the exact same params files when running RosettaCM and had no such errors although it also runs in a centroid mode (although I am not sure if the ligand is part of the calculations in the centroidic stage).

If I add manually to the cen.params file a CEN atom,  I get the following error:

short + medium + long

core.scoring.constraints.ConstraintsIO: read constraints from /dev/shm/hvit33nb/minimize.cst

core.scoring.constraints.ConstraintsIO: Read in 66646 constraints

core.optimization.Minimizer: [ WARNING ] LBFGS MAX CYCLES 1000 EXCEEDED, BUT FUNC NOT CONVERGED!



ERROR: ResidueType OHE does not have an atom CA

ERROR:: Exit from: /home/benchmark/rosetta/source/build/PyRosetta/linux/clang-3.4.2/python-3.6/release/source/src/core/chemical/ResidueType.hh line: 426

Traceback (most recent call last):

File "../trRosetta.py", line 231, in <module>

main()

File "../trRosetta.py", line 175, in main

repeat_mover.apply(pose)

RuntimeError:



File: /home/benchmark/rosetta/source/build/PyRosetta/linux/clang-3.4.2/python-3.6/release/source/src/core/chemical/ResidueType.hh:426

[ ERROR ] UtilityExitException

ERROR: ResidueType OHE does not have an atom CA

It obviously has to do with the centroid mode, because if I add the constraints after switching to fullatom for refinment, the run completes and I get a model with the heme bound in the correct binding site.

Does anyone have an idea what should be modify in the script or params so I will be able to perform the first minimization step with the ligand constraints?

Many thanks,

Shiran.