A pipeline for the parameterisation of stapled peptide residues and for the analysis of their secondary structure preferences via molecular dynamics simulations
We recommend creating separate conda environments for the residue fragmentation, QM torsion scans and MM energy decomposition. For details on how to create and work with conda environments, refer to: https://docs.conda.io/projects/conda/en/latest/user-guide/tasks/manage-environments.html
1. Residue Fragmentation
Refer to https://docs.openforcefield.org/projects/bespokefit/en/stable/getting-started/installation.html for instructions for bespokefit.
conda create -n bespokefit-env
conda activate bespokefit-env
conda install mamba
mamba install -c conda-forge openff-bespokefit
mamba install -c conda-forge ambertools
mamba install -c conda-forge nglview
2. QM Scans
Execute the commands below in the specified order:
conda create -n qm_scans python=3.8
conda activate qm_scans
ambertools 18.0
conda install -c omnia ambertools=18.0
rdkit 2022.09.5
conda install -c conda-forge rdkit=2022.09.5
conda install mamba
psi4 1.6.1
mamba install -c psi4 psi4=1.6.1
psiresp 0.4.2
mamba install -c conda-forge psiresp=0.4.2
papermill 2.5.0
pip install papermill
pip install parmed
After installing the above packages, pydantic will need to be downgraded to 1.10.8
conda install -c conda-forge pydantic=1.10.8
3. MM Energy Decomposition
Refer to https://sire.openbiosim.org/install.html for instructions for Sire. The version of Sire used in this work is 2023.5.1
conda create -n openbiosim "python<3.13"
conda activate openbiosim
conda install -n openbiosim -c conda-forge -c openbiosim sire
conda install matplotlib
conda install rdkit
conda install scikit-learn
4. MD Simulations
Refer to https://ambermd.org/AmberMD.php for installing the latest version of AMBER.
Force Field Library
Contains the force field parameters for the stapled residues in this work, along with peptide PDB templates and tleap scripts to generate MD simulation inputs.
Parameterisation Scripts
Contains code to prepare force field parameters for other stapled residues and/or non-proteinogenic amino acids.
Molecular Dynamics
Contains the SAH-p53 peptide PDB input files and scripts to prepare, run and analyse MD simulations, as well MD trajectories and output from helicity analyses.
TBC
