PEMPNI (Predictors for Effects of Mutations on PNIs) is a computational method that could effectively predict the effects of missense mutations on protein-DNA and protein-RNA interactions. This algorithm includes an energy module and a nonenergy module. The former is based on the novel geometric partition-based energy features, and the latter is based on the structural and sequence features. The integration of multifaceted information could generate more robust predictions.
The ./bin directory contains programs to predict the two types of mutation effects.
The ./datasets directory contains the mutational information of samples in various datasets.
The ./WT_PDB directory contains the PDB files of wild-type structures used in this project.
The ./MT_PDB directory contains the PDB files of mutant structures used in this project.
The ./scripts directory contains auxiliary scripts used in this project.
The ./models directory contains prediction models used in this project.
The ./examples directory contains two examples for protein-DNA/RNA complexes.
The ./software directory contains software lists used in this project.
Perl ( >= 5.0 ) and pdl module
Python ( >= 3.0 ) and scikit-learn, numpy, scipy, math and re modules
GCC ( >= 5.3.0 )
git clone https://github.com/hzau-liulab/PEMPNI.git
To use PEMPNI, you need to conduct the installation of some third-party software, including Amber, Modeller, NACCESS, HBPLUS, ENDES and BLAST.
1.To avoid copyright issues, we only provide the official website of third-party software. Please download and install them by yourself. It is recommended to install all the software in the same directory for modifying the paths.
Amber: http://ambermd.org/index.php
Modeller: https://salilab.org/modeller/
NACCESS: http://wolf.bms.umist.ac.uk/naccess/
HBPLUS: https://www.ebi.ac.uk/thornton-srv/software/HBPLUS/
ENDES: https://sparks-lab.org/publication/ (Paper ID: 098)
BLAST: ftp://ftp.ncbi.nlm.nih.gov/blast/executables/blast+/LATEST/
Nonredundant database: ftp://ftp.ncbi.nlm.nih.gov/blast/db/
2.Related settings of Amber software
Modify the first three lines of ./scripts/GB1/tleap.in and the second line of ./scripts/GB1/amber.sh according to the installation path of Amber software. Conduct the same settings for ./scripts/GB2/tleap.in and ./scripts/GB2/amber.sh.
3.Related settings of other software
Other software should be installed in the same directory and obtain executable permissions. You can refer to the commands as follows.
cd ./software
chmod 777 ./hbplus/hbplus
chmod 777 ./modeller9.25/bin/mod9.25
chmod 777 ./naccess/naccess
chmod 777 ./ncbi-blast-2.11.0+/bin/psiblast
chmod 777 ./ncbi-blast-2.11.0+/bin/blastpgp
chmod 777 ./enrich/processpdb
chmod 777 ./pinup/pinup
Note: Because processpdb and pinup use the blastpgp and nonredundant database, you need to manually modify the sixth line of these two files correspondingly.
You will see protein-DNA.pl and protein-RNA.pl scripts in the ./bin/ directory, and you need to check and modify the paths related to specific software and databases involved in these scripts. For different types of complexes, you need to select the corresponding script.
The input file is the original structure downloaded from the PDB database, and the scripts will automatically process the raw data. You should ensure that the structural file exists in the ./WT_PDB directory.
Please go to the ./bin/ directory, and then run the following command including the information of mutation sites. To run the script, you need to set three parameters, such as the PDB name, chain name and mutation information.
For example
cd ./bin
perl ./protein_DNA.pl 1AAY A D120A >>./log.txt
or
perl ./protein_RNA.pl 1FEU A D87E >>./log.txt
You will obtain all the resulting files in the corresponding directory, and the result.txt file contains the prediction results as follows.
PDB ID:1AAY
Chian ID:A
Position:D120A
Predicted affinity change:0.097
Predicted score:0.135
Significant decrease:NO
Predicted affinity changes are typically in the range of -3 to 5, and positive and negative values correspond to destabilizing and stabilizing effects, respectively. Predicted scores are in the range of 0 to 1, and if this score is greater than 0.47 for MPDs or 0.32 for MPRs, the submitted mutation could significantly decrease binding affinity.
If you have any questions or suggestions about PEMPNI, please contact us by email: jiangyao@webmail.hzau.edu.cn or liurong116@mail.hzau.edu.cn The scripts of this project are free for academic use. For commercial use, please contact with the authors.