This repository contains the codes and scripts for the paper "Resolving Protein Conformational Plasticity and Substrate Binding Through the Lens of Machine-Learning" by Navjeet Ahalawat and Jagannath Mondal (2022) doi: https://doi.org/10.1101/2022.01.07.475334

I am using Anaconda (Python 3.6) and the following packages:

• MSMBuilder 3.8.0.
• PyEMMA 2.5.4
• scikit-learn 0.19.2
• numpy
• matplotlib

• run_pair_distances.sh - bash script to calculate distances between given pairs using msmbuilder package
• contact_pairs.txt - contact pairs used in in msmbuilder
• script_randomforest.py - python script to build the Random Forest Classifier Model
• xgboost.py - python script to build XGBoost model for classification
• selected_pairs2npy.py - Python script to extract the selected pairs identified from RF Classifier
• Top200_residue_pairs - Top 200 pairs from the RF Classifier Model of T4L system
• plot_tica.py - Python script to plot the free energy surface
• plot_tica_fig2.py - Python script to plot the free energy surface
• plot_tica_fig2_new.py - Python script to plot the free energy surface
• plot_tica_fig4.py - Python script to plot the free energy surface
• plot_tica_fig4_new.py - Python script to plot the free energy surface
• traj1_pairs_1-2.tcl - VMD TCL script to visulaize network of the selected pairs
• traj2_pairs_1-2.tcl - VMD TCL script to visulaize network of the selected pairs
• traj3_pairs_1-2.tcl - VMD TCL script to visulaize network of the selected pairs
• t4l_image.com - UCSF Chimera script to visulaize the T4L protein

1. Prepare raw collective varibale using msmbuilder script.
2. Catenate all the numpy files and rename it to X_3_trajs.npy
3. Calculate distance between cavity COM and ligand (benzene) COM
4. Catenate all distance files in the same order of X_3_trajs.npy and convert it into binary format 0 and 1 using distance cutoff criteria. Rename this file as Y_3_trajs.npy.
5. Build RF Classifier Model using script_randomforrest.py
6. Use this model for further analysis

$ vmd -e traj1_pairs_1-2.tcl ref.pdb

$ vmd -e traj2_pairs_1-2.tcl ref.pdb

$ vmd -e traj3_pairs_1-2.tcl ref.pdb