Active Site Modeling and Clustering (ASMC)

ASMC combines (i) homology modeling of family members (MODELLER), (ii) ligand-binding pocket search (P2RANK), (iii) structural alignment of modeled active sites (USalign) and (iv) density-based spatial clustering of obtained alignments (DBSCAN) in a single command line. Clustering step can be carried out on either structural or sequence alignment.

Installation

Download

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

Python requirements

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

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

pip

pip install ./

conda or mamba

conda env create -n env_name -f env.yml

The command pip install ./, create the asmc command and adds it the User PATH environment variable. We therefore recommend that you also use this command after installation via conda or mamba.

It's recommended to use the pip install ./ command after the installation via conda or mamba. Indeed, this creates asmc command and adds it to the User PATH envrionment variable.

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 (or it's name if the location is in the PATH)
• the path of USalign executable (or it's name if the location is in the PATH)

Example:

distances: "/home/User/ASMC/resources/AA_distances.tsv"
usalign: "USalign"  # location in the PATH e.g: /usr/bin ...
p2rank: "/home/User/p2rank_2.4.1/prank"  # another location

The keys should be identical to this example.

Quick Usage

Run ASMC in a blind way (unknown active site) using a multi fasta file that should contain at least 100 sequences for clustering to be sufficiently relevant.

asmc run --log run_asmc.log --threads 6 -r reference_file -s sequences.fasta

reference_file should contains the path to the reference(s) structure(s), e.g:

<path>/RefA.pdb
<path>/RefB.pdb

NB: For more details, see the wiki