Data from: SEEKR2: Versatile Multiscale Milestoning Utilizing the OpenMM Molecular Dynamics Engine

Please cite as:

Votapka, L. W.; Stokely, A. M.; Ojha, A. A.; Amaro, R. E. Data from: SEEKR2: Versatile Multiscale Milestoning Utilizing the OpenMM Molecular Dynamics Engine. https://doi.org/10.6075/J0668DDR

Corresponding author:

Rommie E. Amaro − University of California, San Diego, La
Jolla, California 92093, United States; orcid.org/0000-
0002-9275-9553; Email: ramaro@ucsd.edu

Primary associated publication:

Votapka, L. W.; Stokely, A. M.; Ojha, A. A.; Amaro, R. E. SEEKR2: Versatile Multiscale Milestoning Utilizing the OpenMM Molecular Dynamics Engine. J. Chem. Inf. Mod. In Review. https://doi.org/10.33774/chemrxiv-2021-pplfs

Description of contents:

This data set contains the files necessary to recreate the results
in the paper "SEEKR2: Versatile Multiscale Milestoning Utilizing the 
OpenMM Molecular Dynamics Engine".

Methods:

Important note: some of the larger outputs of MD and BD simulations
have been removed to save space, and could be regenerated if needed.
However, this dataset should contain the contents needed to
recreate the SEEKR2 analysis of kinetics and thermodynamics 
properties for the trypsin/benzamidine and host/guest systems.

Table of Contents:
I. Recreate the Trypsin/Benzamidine results
II. Recreate the Host/Guest results
III. View transition matrices
IV. Recreate the JAK2 Results

I. Recreate the Trypsin/Benzamidine results

In order to recompute the kinetics and thermodynamics of trypsin/
benzamidine binding and confirm the results in the SEEKR2 manuscript,
you will need to have SEEKR2 fully installed.

Please see the SEEKR2 Github repository at 
https://github.com/seekrcentral/seekr2.git and the associated 
documentation at https://seekr2.readthedocs.io/en/latest/ 
for installation instructions.

Note: installation of OpenMM, Browndye2, and NAMD2 not required
to analyze the data output, only if you want to re-run the 
simulations.

To run the analysis, enter the following command from the seekr2/seekr2/
directory.:

$ python analyze.py /PATH/TO/seekr2_data/tryp_ben_mmvt_seekr/model.xml

You will need to enter the path to the seekr2_data directory in the 
command above.

If all went correctly, you should see an output that displays the k-on,
k-off, and other quantities. Images should also be written to
seekr2_data/tryp_ben_mmvt_seekr/images_and_plots.

To perform a convergence analysis, then use the converge.py program:

$ python converge.py /PATH/TO/seekr2_data/tryp_ben_mmvt_seekr/model.xml

Convergence output will be produced, and convergence images will be 
generated.


II. Recreate the Host/Guest results

As with the trypsin/benzamidine system above, one may run analyze.py 
and converge.py on any of the host/guest with the model.xml file as
the program argument.

For instance, within the seekr2/seekr2/ directory, one may compute
the kinetics and thermodynamics of the 1-butanol system:

$ python analyze.py /PATH/TO/seekr2_data/hostguest_mmvt/BCD_1-propanol/model.xml
$ python converge.py /PATH/TO/seekr2_data/hostguest_mmvt/BCD_1-propanol/model.xml

However, in order to generate the ranked plots which compare the computed
quantities between host/guest systems, I've included the following program
within the seekr2_data/ directory:

$ python plot_all_hostguest_systems.py

This command should produce a series of plots which rank the different
host/guest systems by k-off, k-on, and free energy of binding.


III. View transition matrices

If you wish to view the transition matrices for the SEEKR2 calculation, 
Use the following python script at the matrices will be printed to the
screen (in this case, for trypsin/benzamidine, but you can substitute 
any other system's model.xml file):

$ python print_rate_matrix_Q.py tryp_ben_mmvt_seekr/model.xml

With slight modifications to this script, just about any other quantity 
of interest may be extracted from the SEEKR2 API


IV. Recreate the JAK2 Results

As with the trypsin/benzamidine system above, one may run analyze.py 
and converge.py on any of the JAK2 systems with the model.xml file as
the program argument.

For instance, within the seekr2/seekr2/ directory, one may compute
the kinetics and thermodynamics of the first JAK2 system:

$ python analyze.py /PATH/TO/seekr2_data/jak_systems/jak_lig_6_0/model.xml
$ python converge.py /PATH/TO/seekr2_data/jak_systems/jak_lig_6_0/model.xml

Technical details:

SEEKR2 v2.5.1-beta
Python 3.8
Numpy 1.22.3
Scipy 1.7.3
matplotlib 3.5.2

License:

MIT License: https://github.com/seekrcentral/seekr2/blob/master/LICENSE