Alanine Scanning module

Submodules

Module contents

HADDOCK3 module for alanine scan.

This module is responsible for the alanine (or any other residue) scan analysi of the models generated in the previous step of the workflow. For each model, the module will mutate the interface residues and calculate the energy differences 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

Therefore, a positive delta_score indicates that the mutation is destabilizing while a negative delta_score indicates that the mutation is stabilizing.

If cluster information is available, the module will also calculate the average energy 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

  • 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]
class haddock.modules.analysis.alascan.HaddockModule(order, path, *ignore, init_params=PosixPath('/opt/hostedtoolcache/Python/3.10.17/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'

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

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’]
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

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