perses-barnase-barstar-paper

Contains scripts, input files, and data for:

• Running and analyzing relative free energy calculations for terminally-blocked amino acids and barnase:barstar using Perses
• Identifying and characterizing slow degrees of freedom

Publication: https://pubs.acs.org/doi/full/10.1021/acs.jctc.3c00333

Clarifications

• In Figures 4, S6, S10, S14, the DDGs for the reverse mutations were multiplied by -1 to allow for comparison with experiment.
• In Figures 4 and S10, the labeling of data points may be confusing. It is easiest to interpret the "-(Q83R)" label as "Q83R".
• In Table S1 (and the rest of the tables in `perses-barnase-barstar-paper/data/"), the DDGs for the reverse mutations were not multiplied by -1.

Contributors

• Ivy Zhang
• Dominic Rufa

License

• This software is licensed under the MIT license - a copy of this license is provided as SOFTWARE_LICENSE
• The data in this repository is made available under the Creative Commons CC0 (“No Rights Reserved”) License - a copy of this license is provided as DATA_LICENSE

Manifest

• data/ - Contains the data necessary to reproduce the figures and bash scripts used to run the jobs
• envs/ - Contains the dumps of the conda environments used in this study
• input_files/ - Contains all input PDB files and relevant scripts for generating/modifying the PDBs
• scripts/ - Contains all Python scripts for solvating, parametrizing, running equilibration, generating free energy calculation input files, running alchemical replica exchange (AREX), and running alchemical replica exchange with solute tempering (AREST).

Environment

Core dependencies include Perses 0.10.1, OpenMMTools 0.21.5, MDTraj 1.9.7, and pymbar 3.1.1.

OpenMM 8.0.0beta (build 0), a development version of OpenMM 7, was used to generate the input files for alchemical replica exchange (AREX) and alchemical replica exchange with solute tempering (AREST), run equilibration, and run AREX for the terminally-blocked amino acids. The conda environment including this version of OpenMM is called perses-paper3.

OpenMM 7.7.0.dev2, a development version of OpenMM 7 which was built after OpenMM 8.0.0beta and contains a performance enhancement for AREX and AREST, was used for all other AREX and AREST simulations. The conda environment including this version of OpenMM is called perses-paper5. This environment was also used to conduct all analysis.

$\Delta\Delta G$ comparison plots were generated with cinnabar 0.3.0. All other plots were generated using Matplotlib 3.5.2.

The environment files for perses-paper3 and perses-paper5 are located in envs/. They can be used to create a new environment by:

mamba create -n new-env
mamba install --name new-env --file perses-paper5-explicit.txt

where new-env is an environment name of your choice.

Alternatively, the environments can be created using the following commands:

perses-paper3:

mamba create -n perses-paper3 -c conda-forge/label/openmm_rc -c conda-forge -c openeye openmm=8.0.0beta openmmtools=0.21.5 pymbar=3.1 jupyter perses=0.10.1 openff-toolkit openeye-toolkits cudatoolkit=10.2  clusterutils mpi mpi4py mpich=3.4 mpiplus rich yank python=3.9

perses-paper5:

mamba create -n perses-paper5 -c conda-forge/label/openmm_dev -c conda-forge -c openeye openmm=7.7.0dev2 openmmtools=0.21.5 pymbar=3.1 jupyter perses=0.10.1 cinnabar=0.3.0 openff-toolkit openeye-toolkits cudatoolkit=10.2  clusterutils mpi mpi4py mpich=3.4 mpiplus rich yank python=3.9