READ ME - Project Scripts

Here, we provide the scripts used to generate partial charges, assess variability, and run absolute hydration free energy calculations.

Instructions

Install the two conda environments needed for this project.

1. Create openfe environment from openfe.yaml
   • mamba create -f openfe.yaml
   • This environment should be used with the following scripts
     • charge_molecules.py
     • calculate_bond_dq.py
     • prep_fe_am1bcc.py
     • prep_fe_elf10.py
     • prep_fe_nagl_pt2.py
2. Create nagl environment from nagl.yaml
   • mamba create -f nagl.yaml
   • This environment should be used with the following scripts
     • prep_fe_nagl_pt1.py

Bulk charging molecules

These are the scripts used to generate 50 random conformers of a molecule and charge them using various partial charge generation methods.

• charge_molecules.py
  • given toolkit='openeye' and charge_method=am1bcc
    • should be run with environment created from openfe.yaml
    • charges molecules using either OpenEye AM1-BCC charges or AmberTools AM1-BCC charges
    • We generate 50 random conformers
    • We charge each conformer using the chosen AM1-BCC charge toolkit
  • given toolkit='ambertools' and charge_method=am1bcc
    • should be run with environment created from openfe.yaml
    • charges molecules using either OpenEye AM1-BCC charges or AmberTools AM1-BCC charges
    • We generate 50 random conformers
    • We charge each conformer using the chosen AM1-BCC charge toolkit
  • given toolkit='openeye' and charge_method=am1bccelf10
    • should be run with environment created from openfe.yaml
    • charges molecules using OpenEye AM1-BCC ELF10 charges
    • We generate 50 sets of 500 random conformers
      • Each set has a different random seed
    • Each set of 500 conformers is used as an input to AM1-BCC ELF10 charge generator
    • This results in 50 AM1-BCC ELF10 partial charge sets
  • given toolkit='openff' and charge_method=nagl
    • should be run with environment created from nagl.yaml
    • charges molecules uisng OpenForceField's NAGL charges
    • We generate 50 random conformers
      • this is in way unnecessary because NAGL charges should be conformer independent
      • however, this allows us to prove NAGL charges are conformer indpendent

Preparation of absolute hydration free energy calculations

• AM1-BCC charges
  • prep_fe_am1bcc.py
    • should be run with environment created from openfe.yaml
    • prepares OpenFE absolute hydration free energy calculation start files with AM1-BCC charges
    • uses either OpenEye or AmberTools to charge molecules
    • each replicate of the calculation will be identical except in the assigned partial charges
      • each replicate will have partial charges generated from a random conformer
      • each replicate will begin the simulation from the same 3D coordinates / conformer
• AM1-BCC ELF 10 charges
  • prep_fe_elf10.py
    • should be run with environment created from openfe.yaml
    • prepares OpenFE absolute hydration free energy calculation start files with OpenEye AM1-BCC ELF10 charges
    • each replicate of the calculation will be identical except in the assigned partial charges
      • each replicate will have partial charges generated from a set of 500 random conformers
      • each replicate will begin the simulation from the same 3D coordinates / conformer
• OpenFF NAGL charges
  • prep_fe_nagl_pt1.py
    • should be run with environment created from nagl.yaml
      • it is necessary to use a separate environment to generate the charges as the OpenFF toolkit version necessary to use NAGL is incompatible with the version of OpenFE used to create the simulations start files
    • generates NAGL charges and saves the charges in a .mol2
    • We generate 50 random conformers
      • this is in way unnecessary because NAGL charges should be conformer independent
      • however, this allows us to prove NAGL charges are conformer indpendent
  • prep_fe_nagl_pt2.py
    • should be run with environment created from openfe.yaml
    • prepares OpenFE absolute hydration free energy calculation start files with OpenFF NAGL charges
      • requires the .mol2 files generated from prep_fe_nagl_pt1.py
    • each replicate of the calculation will be exactly identical including in the assigned partial charges as NAGL is a conformer independent charge generation method

Generation of figures

• plot_2dmol_with_qdiff.ipynb
  • Creates a 2D image of the molecule
  • User selects 2 partial charge sets to compare
  • Notebook highlights each atom based on the partial charge difference for that atom between the 2 partial charge sets
• plot_2dmol_with_bonddqdiff.ipynb
  • Creates a 2D image of the molecule
  • User selects 2 partial charge ∆q_bond sets to compare
  • Notebook highlights each bond based on the ∆q_bond difference for that bond between the 2 partial charge ∆q_bond sets