RNA Scanning module

Submodules

Module contents

HADDOCK3 module for RNA base scan.

This module performs a mutagenesis scan of RNA bases for the model(s) generated in the previous step of the workflow. For each model, every selected interface nucleic acid residue is mutated into each of the four RNA bases (A, C, G and U) and the differences in the haddock score and its individual components between the wild type and each mutant are calculated, thus providing a measure of the impact of such mutations. By default, all four possible bases are tested for every selected interface nucleotide (the wild-type base is skipped). Such difference (delta_score) is always calculated as:

delta_score = score_wildtype - score_mutant

As the score are typically negative with lower values being better, a _positive_ delta_score indicates that the mutation is stabilizing while a _negative_ delta_score indicates that the mutation is destabilizing.

If cluster information is available, the module will also calculate the average haddock score difference for each cluster of models. For each mutation, a Z score is calculated as:

Z = (delta_score - mean) / std

where mean and std are the mean and standard deviation of the delta_score over all the mutations.

The module will also generate plots of the RNA scan data, showing the distribution of the delta_score (and every component) for each mutation at the interface.

You can use the parameters below to customize the behavior of the module:

  • scan_bases: list of target bases to be tested for each nucleotide. By default all four RNA bases (A, C, G, U) are tested.

  • chains: list of chains to be considered for the RNA scan. In some cases you may want to limit the analysis to a single chain.

  • output_mutants: if True, the module will output the models with the mutations applied (only possible if there is only one model)

  • output_bfactor: if True, the module will output the non-mutated models with the rescaled delta_score in the B-factor column

  • plot: if True, the module will generate plots of the RNA scan data

  • splitplot: if True, the scan plot shows one panel per energy component; if False (default) all components are overlaid in a single panel

  • resdic: list of residues to be used for the scanning. An example is:

>>> resdic_A = [1,2,3,4]
>>> resdic_B = [2,3,4]

Only nucleic acid (RNA) residues at the interface are mutated; protein and other residues are ignored.

When applying a mutation, the ribose-phosphate backbone is always kept. For mutations between bases of the same ring type (purine <-> purine, i.e. A <-> G, or pyrimidine <-> pyrimidine, i.e. C <-> U), the shared base ring atoms are also kept so that the base orientation is preserved and CNS only rebuilds the differing substituents. For cross-type mutations (purine <-> pyrimidine), the three glycosidic-region anchor atoms are kept and renamed to their counterpart in the target ring system (pyrimidine N1/C2/C6 <-> purine N9/C4/C8), so that the base orientation is preserved and CNS rebuilds the rest of the new base.

class haddock.modules.analysis.rnascan.HaddockModule(order, path, *ignore, init_params=PosixPath('/opt/hostedtoolcache/Python/3.10.20/x64/lib/python3.10/site-packages/haddock/modules/analysis/rnascan/defaults.yaml'), **everything)[source]

Bases: BaseHaddockModule

HADDOCK3 module for RNA base scan.

classmethod confirm_installation()[source]

Confirm if module is installed.

name: str = 'rnascan'
validate_ouput_mutant_parameter(nmodels: int) None[source]

Validate the output mutant parameter.

This parameter can be set to True if only one input model is provided, otherewise we risk to generate too many PDB files.

Parameters:

nmodels (int) – Number of input models.

Default Parameters

Easy

chains

default: []
type: list
title: ChainIDs to be considered for the scanning.
short description: ChainIDs to be considered for the scanning.
long description: ChainIDs to be considered for the scanning. If empty, all the chains will be considered. If not empty, only residues part of the specified chains will be mutated. Do not use this parameter if you are using the resdic_* parameter.
group: analysis
explevel: easy

int_cutoff

default: 5.0
type: float
title: Distance cutoff (Å) used to define interface contacts.
min: 1.0
max: 20.0
short description: Distance cutoff (Å) used to define interface contacts between two interacting molecules.
long description: Distance cutoff (Å) used to define interface contacts between two interacting molecules.
group: analysis
explevel: easy

ligand_param_fname

default: ‘’
type: file
title: Custom ligand parameter file
short description: Ligand parameter file in CNS format
long description: Ligand parameter file in CNS format, for any ligand/residues/molecules not supported by default by HADDOCK.
group: force field
explevel: easy

ligand_top_fname

default: ‘’
type: file
title: Custom ligand topology file
short description: Ligand topology file in CNS format
long description: Ligand topology file in CNS format containing the ligand topologies (atoms, masses, charges, bond definitions…) for any ligand not supported by default by HADDOCK
group: force field
explevel: easy

output_bfactor

default: False
type: boolean
title: Dump the input models with the rescaled delta_score written in the b-factor column.
short description: Dump the input models with the rescaled delta_score written in the b-factor column.
long description: Dump the input models with the rescaled delta_score written in the b-factor column. Those files do not contain the mutations, but rather will display the normalized (between 0 and 100) delta HADDOCK score (100 * (delta_score - min_score) / (max_score - min_score)), averaged over the tested bases, in the b-factor column. The higher the b-factor, the more favourable (or less unfavourable) the mutations. You can color the PDB files according to this attribute (in pymol, type “spectrum b”)
group: analysis
explevel: easy

output_mutants

default: False
type: boolean
title: Dump the mutated, energy-minimized PDB files.
short description: Dump the mutated, energy-minimized PDB files.
long description: Dump the mutated, energy-minimized PDB files. As the number of mutants can be very large, this option is allowed only when a single model is provided in input.
group: analysis
explevel: easy

plot

default: False
type: boolean
title: Plot scanning data.
short description: Plot scanning data.
long description: Plot scanning data.
group: analysis
explevel: easy

scan_bases

default: [‘A’, ‘C’, ‘G’, ‘U’]
type: list
title: List of target RNA bases to test for each nucleotide.
short description: List of target RNA bases tested for each selected interface nucleotide.
long description: List of target RNA bases (A, C, G, U) to be tested for each selected interface nucleotide. By default all four bases are tested. The wild-type base is automatically skipped for each nucleotide.
group: analysis
explevel: easy

splitplot

default: False
type: boolean
title: Split the scan plot into one panel per energy component.
short description: One plot panel per energy component.
long description: If true, the scan plot shows one separate panel per energy component (HADDOCK score, van der Waals, electrostatics and desolvation). If false, all components are overlaid in a single panel.
group: analysis
explevel: easy

Expert

resdic

default: []
type: list
title: List of residues to be mutated
short description: List of residues to be mutated. By default all the interface nucleotides are mutated.
long description: List of residues to be mutated. By default all the interface nucleotides are mutated. resdic_* is an expandable parameter. You can provide resdic_A, resdic_B, resdic_C, etc, where the last capital letter is the chain identifier.
group: analysis
explevel: expert