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GrowLigand

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GrowLigand
#1

Hi all,

Anyone with experience with the GrowLigand mover?

I have as input a holo.pdb structure with a protein target of interest and a small molecule inhibitor which binds with low affinitty (parametrized to be used with genpot). 

I was hopping that this mover would return possible modifications on the ligand so I could rationalize my next steps of synthesis.

Here is my RosettaScripts:

<ROSETTASCRIPTS>
  <SCOREFXNS>
     <ScoreFunction name="beta_cart" weights="beta_cart"/>
  </SCOREFXNS>

  <RESIDUE_SELECTORS>
     <Chain name="chA" chains="A"/>
     <Chain name="chX" chains="X"/>
  </RESIDUE_SELECTORS>


  <TASKOPERATIONS>
  </TASKOPERATIONS>

  <FILTERS>
     <Ddg name="ddg" scorefxn="beta_cart" jump="1" repeats="5" repack_bound="true" repack_unbound="true" relax_bound="false" relax_unbound="true" confidence="0"  />

  </FILTERS>

  <MOVERS>
    <FastRelax name="relax" scorefxn="beta_cart" disable_design="true" repeats="1" dualspace="true" bondangle="false" bondlength="false" min_type="lbfgs_armijo_nonmonotone"/>
    <GrowLigand name="grow" chain="X"/>

</MOVERS>

<PROTOCOLS>
        <Add mover="relax" />
        <Add mover="grow" />
        <Add mover="relax" />
        <Add filter="ddg" />
</PROTOCOLS>
<OUTPUT scorefxn="beta_cart"/>
</ROSETTASCRIPTS>

 

But when I run RosettaScripts it returns a segmentation fault error.

Here is the ROSETTACRASH.log file:

 

##############################################################################################################
#
# Rosetta crash log.
#

[START_CRASH_REPORT]
[ROSETTA_VERSION]: 2019.35+release.767c1ea
[COMMIT_DATE]: 2019-08-30T10:52:08.483471
[APPLICATION]: /home2/allan/softwares/rosetta/rosetta_src_2019.35.60890_bundle/main/source/bin/rosetta_scripts.mpi.linuxgccrelease
[MODE]: Release
[EXTRAS]: mpi (OpenMPI 1.8.3)
[OS]: GNU/Linux
[COMPILER]: GCC version "4.8.5 20150623 (Red Hat 4.8.5-4)"
[STDLIB]: libstdc++ version 20150623
[START_OPTIONS]
 -in:path:database=/home2/allan/softwares/rosetta/rosetta_src_2019.35.60890_bundle/main/database/ -in:file:s=run1.holo_0001.pdb -in:file:extra_res_fa=fluopyramAddedCharges.params -out:overwrite -out:prefix=grow1. -out:mute=core basic protocols.relax checkpoint -out:file:scorefile=growLigand.sc -parser:protocol=/home2/allan/work/2019/LGE/MpOAX/growLigand/growLigand.xml -corrections:beta -corrections:gen_potential

[END_OPTIONS]

[START_BACKTRACE]: RAW_LIBC
/home2/allan/softwares/rosetta/rosetta_src_2019.35.60890_bundle/main/source/build/src/release/linux/3.10/64/x86/gcc/4.8/mpi/libutility.so(utility::save_crash_report(char const*, std::string const&, int)+0x25) [0x7f58b9c32535]
/home2/allan/softwares/rosetta/rosetta_src_2019.35.60890_bundle/main/source/build/src/release/linux/3.10/64/x86/gcc/4.8/mpi/libutility.so(utility::signal_handler(int)+0xaa) [0x7f58b9c3266a]
/lib64/libc.so.6(+0x35670) [0x7f58b728a670]
/home2/allan/softwares/rosetta/rosetta_src_2019.35.60890_bundle/main/source/build/src/release/linux/3.10/64/x86/gcc/4.8/mpi/libprotocols_h.5.so(protocols::ligand_docking::GrowLigand::apply(core::pose::Pose&)+0xe3) [0x7f58c455a2f3]
/home2/allan/softwares/rosetta/rosetta_src_2019.35.60890_bundle/main/source/build/src/release/linux/3.10/64/x86/gcc/4.8/mpi/libprotocols.1.so(protocols::rosetta_scripts::ParsedProtocol::apply_mover(core::pose::Pose&, protocols::rosetta_scripts::ParsedProtocol::MoverFilterPair const&)+0x26d) [0x7f58bf45d65d]
/home2/allan/softwares/rosetta/rosetta_src_2019.35.60890_bundle/main/source/build/src/release/linux/3.10/64/x86/gcc/4.8/mpi/libprotocols.1.so(protocols::rosetta_scripts::ParsedProtocol::sequence_protocol(core::pose::Pose&, __gnu_cxx::__normal_iterator<protocols::rosetta_scripts::ParsedProtocol::MoverFilterPair const*, std::vector<protocols::rosetta_scripts::ParsedProtocol::MoverFilterPair, std::allocator<protocols::rosetta_scripts::ParsedProtocol::MoverFilterPair> > >)+0x3b) [0x7f58bf45e95b]
/home2/allan/softwares/rosetta/rosetta_src_2019.35.60890_bundle/main/source/build/src/release/linux/3.10/64/x86/gcc/4.8/mpi/libprotocols.1.so(protocols::rosetta_scripts::ParsedProtocol::apply(core::pose::Pose&)+0x1cf) [0x7f58bf45f14f]
/home2/allan/softwares/rosetta/rosetta_src_2019.35.60890_bundle/main/source/build/src/release/linux/3.10/64/x86/gcc/4.8/mpi/libprotocols.1.so(protocols::jd2::JobDistributor::run_one_job(std::shared_ptr<protocols::moves::Mover>&, long, std::string&, std::string&, unsigned long&, unsigned long&, bool)+0xb88) [0x7f58bf56dd58]
/home2/allan/softwares/rosetta/rosetta_src_2019.35.60890_bundle/main/source/build/src/release/linux/3.10/64/x86/gcc/4.8/mpi/libprotocols.1.so(protocols::jd2::JobDistributor::go_main(std::shared_ptr<protocols::moves::Mover>)+0xc1) [0x7f58bf56fa11]
/home2/allan/softwares/rosetta/rosetta_src_2019.35.60890_bundle/main/source/build/src/release/linux/3.10/64/x86/gcc/4.8/mpi/libprotocols.1.so(protocols::jd2::MPIWorkPoolJobDistributor::slave_go(std::shared_ptr<protocols::moves::Mover>)+0x5a) [0x7f58bf59053a]
/home2/allan/softwares/rosetta/rosetta_src_2019.35.60890_bundle/main/source/build/src/release/linux/3.10/64/x86/gcc/4.8/mpi/libprotocols.1.so(protocols::jd2::MPIWorkPoolJobDistributor::go(std::shared_ptr<protocols::moves::Mover>)+0x187) [0x7f58bf592c97]
/home2/allan/softwares/rosetta/rosetta_src_2019.35.60890_bundle/main/source/bin/rosetta_scripts.mpi.linuxgccrelease() [0x401f3b]
/lib64/libc.so.6(__libc_start_main+0xf5) [0x7f58b7276b15]
/home2/allan/softwares/rosetta/rosetta_src_2019.35.60890_bundle/main/source/bin/rosetta_scripts.mpi.linuxgccrelease() [0x4021c5]

[END_BACKTRACE]

[FILE]: SIGSEGV
[LINE]: 11
[START_MESSAGE]
Segmentation Fault

[END_MESSAGE]
[END_CRASH_REPORT]

 

 

Any help on how to use this mover properly?

 

Állan.

Category: 
Post Situation: 
Sat, 2019-10-19 05:32
allan.ferrari

GrowLigand was part of an experimental attempt at small molecule generation in Rosetta. That approach has long since been abandoned. There really isn't much support for it anymore, and there wasn't much of a working protocol for it even when it was being developed.

If I had to guess, I'd say your error is related to the fact that there aren't any ligand fragments in the standard ResidueTypeSet, which the GrowLigand mover needs to figure out what it will be adding to your ligand. It looks like you'd need to add ResidueTypes with a FRAGMENT property to the ResidueTypeSet (e.g. with the -extra_res_fa flag), but I'm not sure the details about how those should be constructed.

Mon, 2019-11-04 13:39
rmoretti

Hi Rocco, 

 

Thank you for your response. I thought it was a recent implementation. My bad.

Anyway, it's is probably not working because I generated the ligand to work with the generic potential and the GALigandDocking mover which associates different atom types to what was implemented when GrowLigand was written.

I hope there is an effort in the future to generate this kind of application. It would be very helpful to drug design.

Tue, 2019-11-05 16:52
allan.ferrari