autoBAR: Free Energy Simulator with Tinker Software Packages

A light-weighted automation tool for alchemical free energy simulations with the Bennett Acceptance Ratio (BAR) method using the polarizable AMOEBA and AMOEBA+ force fields.

Prerequisite

• python modules: ruamel.yaml and numpy. (Hint: one can use pip or conda to install easily)
• compiled software: Tinker and Tinker9. (Note: Nothing need to do for Ren lab members).

How to setup

Prepare the following 4 files:

• gas_xyz: ligand tinker xyz file
• box_xyz: ligand or ligand-protein in water, with box info. in the second line
• parameters: Tinker parameter file (see Notes for one-step perturbation function)
• settings.yaml: settings read by autoBAR.py program. Please refer to the example file here.

Note: User customized tinker key files are supported (see here)

How to run

To make it flexible to use, this program was designed to be run in either interactive or automated mode. In the interactive mode, an individual step can be run depending on the requirement. In the automated mode, this program will automatically go through all steps until it exits.

• Interactive mode

  # Run `setup`: generate the necessary input files for Tinker
  python autoBAR.py setup
  # Run `dynamic`: do molecular dynamics simulations at a series of lambda using Tinker/Tinker9
  python autoBAR.py dynamic
  # Run `bar`: do bar analysis using Tinker/Tinker9 after the above MD jobs finish
  python autoBAR.py bar
  # Run `result`: summarize and printout the bar analysis result
  python autoBAR.py result

• Automated mode

  # Run `auto`: automatically run all the above commands
  python autoBAR.py auto

• Advanced feature

   # Run `opt`: use one-step BAR to get numerical gradient of the FE w.r.t. tuning parameters, and optimize the FF parameters. The settings.yaml needs to be setup carefully!
   python autoBAR.py opt

Examples

Two example systems are located in examples folder. They should be easy to read and understand.

• For the Ion-HFE system, only the liquid phase is necessary

   ├── liquid
   ├── Na-water.xyz
   ├── Na.xyz
   ├── result.txt
   ├── settings.yaml
   └── water03.prm
  

• For the Phenol-HFE system, both the liquid and gas phases are needed

   ├── amoeba09.prm
   ├── gas
   ├── liquid
   ├── phenol_solv.xyz
   ├── phenol.xyz
   ├── result.txt
   └── settings.yaml
  

Notes

• Minimal settings for HFE simulations

  • lambda_window: courser # This reduces the number of windows without losing much accuracy
  • liquid_md_total_time: 1.25 ns # The last 4/5 of trajectories (1 ns) is used in BAR
  • liquid_md_time_step: 2.0 fs # Good with RESPA integrator
  • gas_md_total_time: 1.25 ns # The last 4/5 of trajectories (1 ns) is used in BAR
  • gas_md_time_step: 0.1 fs # Gas phase stochastic dynamics

• One-step perturbation is supported

  • An {fname}.prm_ file with small parameter perturbation need to be in the working directory
  • No need modify the settings.yaml file
  • This will be treated as the end state (two end states if involving two legs)