Alanine Scanning module

Submodules

haddock.modules.analysis.alascan.scan module

Module contents

HADDOCK3 module for alanine scan.

This module is responsible for the alanine (or any other residue) scan analysis of the model(s) generated in the previous step of the workflow. For each model, this module will mutate the interface residues and calculate the differences in the haddock score and its individual components between the wild type and the mutant, thus providing a measure of the impact of such mutation. 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 amino acid, 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 amino acids.

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

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

chains: list of chains to be considered for the alanine 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 alanine 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

scan_residue: the residue to scan (default is ‘ALA’)

resdic: list of residues to be used for the scanning. An example is:
>>> resdic_A = [1,2,3,4]
>>> resdic_B = [2,3,4]

For more details about this module, please refer to the haddock3 user manual

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

Bases: BaseHaddockModule

HADDOCK3 module for alanine scan.

classmethod confirm_installation()[source]: Confirm if module is installed.

name: str = 'alascan'

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)) in the b-factor column. The higher the b-factor, the more favourable (or less unfavourable) the mutation. 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_residue

default: ‘ALA’
type: string
title: Residue to be used for the scanning
choices: [‘ALA’, ‘ARG’, ‘ASN’, ‘ASP’, ‘CYS’, ‘GLN’, ‘GLU’, ‘GLY’, ‘HIS’, ‘ILE’, ‘LEU’, ‘LYS’, ‘MET’, ‘PHE’, ‘PRO’, ‘SER’, ‘THR’, ‘TRP’, ‘TYR’, ‘VAL’, ‘ALY’, ‘ASH’, ‘CFE’, ‘CSP’, ‘CYC’, ‘CYF’, ‘CYM’, ‘DDZ’, ‘GLH’, ‘HLY’, ‘HY3’, ‘HYP’, ‘M3L’, ‘MLY’, ‘MLZ’, ‘MSE’, ‘NEP’, ‘PNS’, ‘PTR’, ‘SEP’, ‘TOP’, ‘TYP’, ‘TYS’, ‘CIR’]
short description: Residue to be used for the scanning. The default is alanine.
long description: Residue to be used for the scanning. The default is alanine. Use bigger residues at your own risk.
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 residues are mutated.
long description: List of residues to be mutated. By default all the interface residues 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