Hi, I'm just getting familiar with IMP, looks like a fabulous peace of code! Trying the example in https://integrativemodeling.org/2.4.0/doc/tutorial/kinematics_rrt.html appears to work as intended, however, there are a few questions:
1. I get a warning: WARNING Could not determine CHARMM atom type for atom "HET: C1 " in residue #475 "NAG" so I wonder is there a way to include the sugar topology/parameters in some way - I do seem to recall that the CHARMM FF does have parameters for sugars, at least those found commonly in the PDB.
2. I also get WARNING No CHARMM parameters found for angle S-S-CT2 is this not an interaction that should be there in any CHARMM protein FF?
3. When I include any atom and the corresponding residue into both linker.txt and conect_chains.txt then I get: ERROR: IMP currently does not support switching of parents in a kinematic tree when I do not include the atom numbers (of the corresponding SG atoms) into conect_chains.txt but leave the residues that contain these atoms in linker.txt then it seems to work. What I wonder is: is the tool smart enough to figure out which CYS are S-S bonded on it's own, and account for that during optimization? If not, is there any other way to use S-S bonded cysteins in the linker?
4. I haven't tried out compiling from source yet ... but I'd really like to see whether CUDA gives me any speedup ... is it anywhere documented which parts of the code or which algorithms run on GPU in the current version of IMP?
thanks for any help! regards Michael
rgd question three: I had another look at the output, and it seams that IMP does not account for the S-S bonds in the linker, in some of the output structures the two SG atoms of a di-sulfide bond are far apart from each other (>9Angstrom) ... when I try to account for that by putting the corresponding atom numbers in the conect_chains.txt file then i get the error quoted in the original msg) ... Is there any work-around for this issue? thanks! michael
PS I put a wrong title/header in the original msg, but it seems posts cannot be edited after being sent ...
On 7/2/25 2:13 AM, Michael Brunsteiner via IMP-users wrote: > I'm just getting familiar with IMP, looks like a fabulous peace of code! > Trying the example in https://integrativemodeling.org/2.4.0/doc/tutorial/kinematics_rrt.html > appears to work as intended, however, there are a few questions: > > 1. I get a warning: > WARNING Could not determine CHARMM atom type for atom "HET: C1 " in residue #475 "NAG" > so I wonder is there a way to include the sugar topology/parameters in some way - I do seem to recall that the CHARMM FF does have parameters for sugars, at least those found commonly in the PDB.
rrt_sample needs to know connectivity and radii in order to know what to move and how to score it respectively, and it gets this information from the CHARMM topology and parameter files. To the best of my knowledge the tool hasn't been used on sugars so it might not work at all, but if you want to try it you can certainly add sugar parameters. IMP includes its own copy of the CHARMM 22 forcefield. To see where the files are on your system run from a Python terminal:
import IMP.atom print(IMP.atom.get_data_path('top_heav.lib')) print(IMP.atom.get_data_path('par.lib'))
> 2. I also get > WARNING No CHARMM parameters found for angle S-S-CT2 > is this not an interaction that should be there in any CHARMM protein FF?
In a disulfide bridge (CHARMM DISU patch) both sulfurs have the SM atom type, not S.
> 3. When I include any atom and the corresponding residue into both > linker.txt and conect_chains.txt then I get:
As I understand it these two options work against each other - hinging motion occurs around a linker while connect chains makes a rigid link - so things will get very confused if you try to apply both to the same part of the system.
> What I wonder is: is the tool smart enough to figure out which CYS are S-S bonded on it's own, and account for that during optimization? If not, is there any other way to use S-S bonded cysteins in the linker?
No, the CHARMM topology is not patched. The algorithm also cannot handle cycles IIRC so likely it would get stuck if you were to hack the code to add a DISU patch. I think your only option there would be to treat that part of the system rigidly.
> 4. I haven't tried out compiling from source yet ... but I'd really like to see whether CUDA gives me any speedup ... is it anywhere documented which parts of the code or which algorithms run on GPU in the current version of IMP?
See https://integrativemodeling.org/2.22.0/doc/manual/gpu.html. IMP.kinematics does not include any CUDA code though, so you wouldn't see any speedup there.
Ben
Dear Ben
Thank you so much for your swift/comprehensive answers!
regarding the antibody/IGG modelling, one more question: I understand, with modeller, you can define S-S bonds, and modelling the FC-part plus hinge (including di-sulfide bonds) does work if you have a decent template for the FC (without hinge) - of which there are many. I tried this and it does give the expected result. To get the full length antibody, this would require including the two Fab domains, ideally as rigid bodies. I understand rigid bodies can be defined in modeller, but I wonder: is there a way to define these two Fab domains, and perhaps also the FC, as rigid bodies, have their initial structures be random positions/orientations, and then ask modeller to construct a model of the three domains (one FC, two Fabs) with only the hinge (including the S-S constraints) being sampled, with the constraint that there are supposed to be no overlaps/clashes between the three domains?
I should add, that this random initial position/orientation is important here, since I don't want to bias the algorithm towards any particular conformation (mutual orientation of the 3 domains) and also, I am in the process of generating a large number of structures, and here generating, for each case, a viable initial structure with the three domains positioned/oriented in a physically plausible way would require a lot of manual work using some editor. like pymol or chimera.
best regards, Michael
participants (2)
-
Ben Webb -
Michael Brunsteiner