Awesome

tauRAMD

A collection of Python scripts for computations of relative protein-ligand residence times using tauRAMD (Random Acceleration Molecular Dynamics)

Author: Daria Kokh
Heidelberg Institute of Theoretical Studies (HITS, www.h-its.org)
Schloss-Wolfsbrunnenweg 35
69118 Heidelberg, Germany

Contact: mcmsoft(at)h-its.org

Acknowledgement

EU Human Brain Project (SGA1 and SGA2): This open source software was developed in part in the Human Brain Project funded from the European Union's Horizon 2020 Framework Programme for Research and Innovation under Specific Grant Agreements No 720270 and No. 78907 (Human Brain Project SGA1 and SGA2).

Ligand_swap_out

A set of scripts that helps to swap out ligands in a protein-ligand complex

tauRAMD.py

Script for computation of drug-target relative residence times from Random Acceleration Molecular Dynamics (RAMD)simulations. It also provides statistical analysis of the results.

Prerequisite

To use this script, one has to generate RAMD trajectories. These can be done using GROMACS or NAMD. Tutorials on how to do this can be found below:

For GROMACS tutorial, (please use this GROMACS version gromacs-ramd.)

For NAMD tutorial

1. Multiple (at least 10) RAMD dossociation trajectories must be generated using 
   either Gromacs or NAMD software.
   In the later case script must be modified a bit:  
      soft = "Gr" must be changed to 
      soft = "NAMD"

2. Lines of the output files where ligand dissociation is reported
     for Gromacs: 
         “XX/YYYY.out:==== RAMD ==== GROMACS will be stopped after xxxxx steps.”
     for NAMD: 
         "EXIT: xxxxx  > LIGAND EXIT EVENT DETECTED: STOP SIMULATION"
must ge collected in a single file or in multiple files (if trajectories were started 
from different input coordinate and velocities files)

In addition for the analysis of the interaction fingerprints the following software is required MD-IFP. Please have a look in the MD-IFP examples section for a jupyter notebook that can be run on google colab and one that can be run on ebrains, both require an account at the respective provider.

Usage

tauRAMD.py  input_file[s]

input files must contain a set of lines extracted from the gromacs output. 
Each line contains the number of steps executed before dissociation 
and has the following format: 
        “XX/YYYY.out:==== RAMD ==== GROMACS will be stopped after 874650 steps.”
or if RAMD simulations were done using NAMD software: 
        "EXIT: 462950  > LIGAND EXIT EVENT DETECTED: STOP SIMULATION"

Output

residence time with the standard deviation computed for each input_file and an 
images with representation of the bootstrapping output and statistics