RPOST-3D

A tool for predicting the effects of missense mutation on protein stability changes using 3D structural information of a protein. The tool is based on Direct Message Passing Neural Network (a graph convolutional neural network) and Deep Learning Neural Network. PROST-3D also visualizes and highlights the change in molecular strucutre for a single missense mutation.

Requirements: The requirements.yml file is provided.

Installation of anaconda3 is prerffered

1. create PROST-3D environment from the provided requirements.yml file.

2. Download the following databases and make them ready for searching

   i) uniref50 (https://ftp.uniprot.org/pub/databases/uniprot/uniref/uniref50) [make this ready for blast by using the following command]

              makeblastdb -in uniref50.fasta -dbtype prot -out uniref50
   

   ii) uniclust30_2018_08 (http://wwwuser.gwdg.de/~compbiol/uniclust/2018_08/uniclust30_2018_08_hhsuite.tar.gz)

2.1) Now, set the paths (in line 21-22 in PROST-3D_predict.py) for the installed databases accordingly.

3. Activate your virtual environment(PROST-3D) and run the python script PROST-3D_predict.py

Command-line arguments for the program:

{-pdbid,--pdbid, -pdb_id, --pdb_id} PDB ID of protein from RCSB Protein Data Bank

{-file,--file}	protein sequence (FASTA format)

{-mutation, --mutation}	missence mutation (example: A V 8 I 25 7 or A T 77 H 25 7)

{-mutlist, --mutlist, --ml, --mutation_list}	list of mutations

{-outdir, --outdir, --out_dir}	directory name for results

{-out_file, --out_file, -outfile} Name for the result output file

{-h, --help}	command-line summary

Prediction for a single mutation

python PROST-3D_predict.py -pdb_id RCSB PDB ID --mutation wild-type position mutant-type temp°C(optional) pH(optional) --outdir (optional) Result --out-file (optional) mutation_result

python PROST-3D_predict.py -file Path_To_PDB_Structure --mutation wild-type position mutant-type temp°C(optional) pH(optional) --outdir (optional) Result --out-file (optional) mutation_result

Prediction for list of mutations

python PROST-3D_predict.py -pdb_id RCSB PDB ID -mutlist Path_To_Mutation_List -outdir(optional) Result -out-file(optional) mut_list_Result
   
python PROST-3D_predict.py -file Path_To_PDB_Structure -mutlist Path_To_Mutation_List -outdir(optional) Result -out-file(optional) mut_list_Result

4. Examples of how to run a single mutation and list of mutations

    python PROST-3D_predict.py -pdb_id 1aky --mutation A V 8 I 25 7  --outdir Result -outfile 1aky_prediction
    
    python PROST-3D_predict.py -pdb_id 1aky --mutation-list Input/1aky_mutlist.txt  --outdir Result --out_file 1aky_prediction
   

**Auxiliary files will be stored inside aux_files directory.