RosettaCommons - PyRosetta - General

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Rotamers one- and two-body energies

ajfmdm — Thu, 04 Apr 2024 07:48:26 +0000

Hello! I'm quite new to (Py)Rosetta, so my question may have a very obvious answer, but I tried to find it in many places but couldn't find it, so I figured this was a good place to ask.

My goal is to implement "from scratch" some methods to solve the side-chain optimization problem, using a pairwise-decomposable energy function. In order to do so, I need to have the precomputed one- and two-body rotamer energies . Now, although I managed to calculate these values, I believe I didn't do it in the most efficient way (if it's relevant, what I did was: getting 3 different (equally-spaced) angle values for each chi, for each residue type; for each position in an input pose, I mutated the respective residue to each one of the rotamers; I then calculated the one-body residue energy, and did similarly for pairwise mutated residues energies).

I know this approach is not the best one because: a) it doesn't use Dunbrack's library; b) It's very slow.
In my understanding, Rosetta already has these "rotamer energy matrices" precomputed somewhere (or it precomputes them easily from Dunbrack's library, given a pose), so my question is simply: where is it, and how can I use it?
I think that the information I need is in the pyrosetta/database/rotamer folder, but I really don't know how to use the files there. I tried to look in (Py)Rosetta's source code to see how the files are used, but didn't have much luck there.

If anyone can help me with any information/direction, I really appreciate it.
Thank you so much!

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Design

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Segmentation fault encountered using Interface

WenyuanW — Tue, 02 Apr 2024 20:41:58 +0000

Hi All,

I ran into repeated segmentation fault error when I tried to utilize the InterfaceAnalyzerMover to calcualte interaction energy between the two protein chains.

Here is my script:

import pyrosetta
from pyrosetta.rosetta.core.import_pose import pose_from_file
from pyrosetta.rosetta.protocols.analysis import InterfaceAnalyzerMover
import sys

def calculate_interface_energy(pdb_file, chain_target, chain_partners):
    """
    Calculates the interaction energy between one chain and a complex formed by other chains in a protein structure.
    
    Args:
        pdb_file (str): Path to the PDB file.
        chain_target (str): Identifier for the target chain.
        chain_partners (str): Identifiers for the partner chains concatenated.
        
    Returns:
        float: The interaction energy between the target chain and the partner chains.
    """

    # Load the PDB file into a Pose object
    pose = pose_from_file(pdb_file)

    # Define the complex as a combination of the target chain and partner chains
    complex_identifier = chain_target + "_" + chain_partners

    # Setup the InterfaceAnalyzerMover for the defined complex
    interface_analyzer = InterfaceAnalyzerMover()
    interface_analyzer.set_interface(complex_identifier)
    interface_analyzer.test_move(pose)  # Test the move to ensure the interface is correctly defined
    interface_analyzer.apply(pose)  # Apply the mover to the pose

    # Retrieve the computed interface energy
    interface_energy = interface_analyzer.get_interface_dG()

    return interface_energy


def main():
    # Specify your parameters
    pdb_file = sys.argv[1]
    chain_target = "A"     # The single chain you are focusing on
    chain_partners = "B"  # The other chains, treated as a combined entity

    # Initialize PyRosetta
    pyrosetta.init(extra_options="-mute all -load_PDB_components false -extra_res_fa GDP.params")

    # Calculate and print the interface energy
    interface_energy = calculate_interface_energy(pdb_file, chain_target, chain_partners)
    print(f"Interface energy between chain {chain_target} and chains {chain_partners}: {interface_energy} REU")

if __name__=="__main__":
    main()

The seg-fault error happens with either test_move, or apply (when I comment out test_move)

I can't figure out the problem because it seems to me that the error stems from the underlying C++ script.

Any suggestion is appreciated.

P.S. I cannot attach the test input I used because it is too big and this forum doesn't take the zipped version. If the error cannot be replicated with a different input, I will try to paste the PDB content as plain text in replies.

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In https://github.com/RosettaCommons/PyRosetta.notebooks/blob/master/student-notebooks/06.08-Point-Mutation-Scan.ipynb

What is the meaning of "JUMP" in rigid.RigidBodyTransMover(pose,JUMP)?

lanselibai — Sat, 28 Oct 2023 16:49:48 +0000

There is a unbind function:

def unbind(pose, partners):
    STEP_SIZE = 100
    JUMP = 2
    docking.setup_foldtree(pose, partners, Vector1([-1,-1,-1]))
    trans_mover = rigid.RigidBodyTransMover(pose,JUMP)
    trans_mover.step_size(STEP_SIZE)
    trans_mover.apply(pose)

The system is a three-chain complex, and partners is "HL_A", meaning separating chain H&L from chain A.

If I have a two-chain complex, e.g. partners is "L_R", what should be the value of JUMP?

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Docking

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Minimizing a Symmetric Structure

ammar.x.gilani — Wed, 02 Aug 2023 18:10:50 +0000

Hi, I have a structure with two chains (1 and 2 ) which are identical. My goal is to minimize its structure using FastRelax with a symmetry constraint.

Creating symmetry file:

make_symmdef_file.pl -p Data/2mcg.pdb -a 1 -i 2 > Data/2mcg.symm

Structure minimization:

import pyrosetta
from pyrosetta import rosetta

id = '2mcg'

pose = pyrosetta.pose_from_pdb(f'Data/{id}_symm.pdb')
symm_data = pyrosetta.rosetta.core.conformation.symmetry.SymmData()
symm_data.read_symmetry_data_from_file(f'Data/{id}.symm')
pyrosetta.rosetta.core.pose.symmetry.make_symmetric_pose(pose, symm_data)

rel = rosetta.protocols.relax.FastRelax()
rel.apply(pose)  # Segmentation Fault

But I get segmentation fault at the line specified above.

Moreover, I get the following error when I score the symmetric pose:

import pyrosetta
from pyrosetta import rosetta

id = '2mcg'

pose = pyrosetta.pose_from_pdb(f'Data/{id}_symm.pdb')
symm_data = pyrosetta.rosetta.core.conformation.symmetry.SymmData()
symm_data.read_symmetry_data_from_file(f'Data/{id}.symm')
pyrosetta.rosetta.core.pose.symmetry.make_symmetric_pose(pose, symm_data)

scorefxn = pyrosetta.get_fa_scorefxn()
scorefxn(pose)  # Error Line

RuntimeError: 

File: CountPairFactory.cc:220
[ ERROR ] UtilityExitException
ERROR: Assertion `res2.is_bonded(res1)` failed.

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Symmetry

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How can I automate mutations with PyRosetta or other Rosetta software?

archaeopteryx — Tue, 04 Jul 2023 02:35:40 +0000

I need to create mutant peptides with Rosetta to use in Virtual Screening, the mutations need to be kinda ''random'' (not chosen directly by me) and, if possible, following an evolutionary bias (genetic algorithm). I'm really new at protein modelling and I have only used AlphaFold. Rosetta has many ways to use, and I'm kinda lost, should I use Rosetta Scripts or PyRosetta? Can I do this with both? I haven't found any tutorial that explains how to create mutant peptides following a genetic algorithm with rosetta :( I don't know where to start.

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Chemically Modified Residues

Post-traslational modifications

diegoms — Wed, 21 Jun 2023 08:22:59 +0000

Hello, everyone

I was trying to study the effect of post-translational modifications on the structure of proteins. For that purpose, I followed two different approaches:

I modified the residue with a variant using pyrosetta.rosetta.core.pose.add_variant_type_to_residue. Then, I replaced the original residue with the modified one using pose.replace_residue().
I tried using pyrosetta.rosetta.core.pose.add_variant_type_to_pose_residue to directly modify the residue in the pose.

In both cases, I obtained None as a result, but I would like to obtain a modified pose in order to calculate the ΔΔG value. Does anyone know how I can achieve that? Any suggestions would be appreciated.

Thanks in advance,

Diego

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Different results FastRelax pyrosetta vs rosetta_scripts

karenjgonzalez — Tue, 20 Jun 2023 16:52:08 +0000

Hi everyone,

I want to relax a designed disulfide bond with FastRelax, but when I try to do it in Pyrosetta it seems like it gets no optimization at all. However, when I try FastRelax in rosetta scripts I get a good geometry. Could you please help me identify what I am missing in my Pyrosetta code?

Thank you!

## Pyrosetta
fast_relax = protocols.relax.FastRelax(scorefxn_in=scorefxn, standard_repeats=5)
movemapOptions = core.kinematics.MoveMap()
movemapOptions.set_chi(True); movemapOptions.set_bb(True); movemapOptions.set_jump(True)
fast_relax.set_movemap(movemapOptions)
fast_relax.set_task_factory(taskOper)
fast_relax.apply(pose)
pose.dump_pdb("test.pdb")


## Rosetta_script
<MOVERS>
 <FastRelax name="relax" scorefxn="ref2015" task_operations="init,repackonly,norepack" repeats="5">
    <MoveMap name="moveMap" bb="1" chi="1" jump="1"/>
 </FastRelax>
</MOVERS>

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Post Situation:

Set torsions for atoms in different residues

mluengo — Fri, 12 May 2023 10:07:32 +0000

I am working with a polymer with a non-aminoacidic backbone comprising two subunits, each defined as individual residues. I have already defined the params file for both subunits; however, I am experiencing issues exploring torsions between these connected residues. I am setting the angle movement using pose.conformation().set_torsion_angle(). This function has worked for angles between atoms inside the same subunit. However, when trying to set_torsion_angle() for atoms residing in different residues, I get the following error:

core.kinematics.AtomTree: [ WARNING ] DOF for this torsion angle could not be found in AtomTree. core.conformation.Conformation: set_torsion_angle failed, unable to find dof_id: atomno= 4 rsd= 3 atomno= 1 rsd= 4 atomno= 3 rsd= 4 atomno= 4 rsd= 4

How could I define this DOF in the AtomTree, or is there a way to resolve this issue differently? I am attaching the params files for both subunits.

Attachment	Size
new_TPA.params.txt	2.12 KB
new_ETY.params.txt	1.26 KB

Category:

Non-Canonical Peptides

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Challenge with applying AntibodyCDRGrafter method and MinMover method

kylevaccaro — Sun, 19 Feb 2023 05:41:30 +0000

I've been trying to trial designing antibody CDRs. Thus far I haven't had much luck applying standard methods. I've converted my antibody to AHO scheme with PyIgClassify and applied the cleanATOM method, however, I am still running into the following error prompt. Any recommendations on how to resolve this, would be great.

I've applied the AntibodyInfo method and am able to print the antibody with the sequences of each CDR, so I don't think the first portion about start and end not being contained is correct.

The prompt says I can apply a loop modeling application to fix the issue, so I'm reading a bit about what's possible from the documentation and pyTutorial. Any thoughts or suggested reading is appreciated.

Error Prompt:

Antibody does not contain the start or end residue of cdr loop H1 start: 132 end: 0 Please check pdb is renumbered properly and the passed -numbering_scheme option matches the PDB. This could also mean missing density in the cdr loop. Loop modeling applications can be used to fill missing residues

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