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Introduction

ASMC is a precision tool for deciphering the amino acid diversity that composes the active site of a given homologous protein family.

Selection of reference structure(s)

This step is critical since ASMC relies on the homology modeling step to obtain relevant 3D models, i.e. the structural constraints imposed by the selected reference structure(s) may generate irrelevant models that could ultimately be misclassified. The subsequent goal is to identify interesting 3D conformations of your queried protein within the Protein Data Bank (PDB). Reference structure(s) should be carefully chosen under the biological context (open/close state, monomer, ligands, enzymatic results...) and priority should be given to high-resolution holo structures, namely protein-ligand complexes, since active sites are often better characterized.

Active site pocket

ASMC analyses amino acid diversity of protein active sites either given by the user or directly predicted through the ASMC workflow. We advise users to carefully define their queried active site by selecting its amino acid composition based on their own experience (enzymatic assays, mutation, docking...) or literature.

Installation

Download

Download the latest GitHub release to obtain the code: https://github.com/labgem/ASMC/releases

Python requirements

• Python ≥ 3.8
• numpy
• scikit-learn
• pyyaml
• pillow
• biopython ≥ 1.81
• weblogo

You can install the python dependencies with pip, conda or mamba with the following commands and the files given in the releases:

pip

pip install -r requirements.txt

conda

conda env create -n env_name -f env.yml

mamba

mamba env create -n env_name -f env.yml

Installation via conda and mamba includes the MODELLER installation, but you still need to request the license key.

External Software dependencies

• P2RANK - for ligand-binding pocket detection (https://github.com/rdk/p2rank)
• MODELLER - for homology modeling (https://salilab.org/modeller/)
• USalign - for structural alignment (https://zhanggroup.org/US-align/)

Please follow the links above and the instructions given by their authors.

Configuration

In ASMC/resources, add a file exactly named config_asmc.yml. This file should contain 3 information:

• the path to the ASMC/resources/AA_distances.tsv
• the path of P2RANK executable
• the path of USalign executable

Example:

distances: "/home/User/ASMC/resources/AA_distances.tsv"
usalign: "/home/User/bin/USALIGN/USalign"
p2rank: "/home/User/bin/p2rank_2.4.1/prank"

The keys should be identical to this example.