FEP-SPell-ABFE

FEP-SPell-ABFE: An Open Source Alchemical Absolute Binding Free Energy Calculation Workflow for Drug Discovery

Notable features:

• Support for performing not only ABFE but also AHFE (absolute hydration free energy) prediction when turn on "hfe_only".
• Support AlChemical Enhanced Sampling (so-called ACES: one REST2-like method) by setting "gti_add_sc=5/6".
• Support Replica-exchange method for FEP production simulations, but this requires one lambda window simulation to occupy one GPU card.
• Support for specifying ion concentration condition.
• Support for doing charge correction for charged ligands based on Poisson-Boltzmann algorithm using APBS software.
• Support for running one or more stages ("topology", "equilibration", "alchemy_morph", "alchemy_md", "alchemy_analysis") in one submit.
• Support local parsimonious: the simulations of stages ("equilibration", "alchemy_md") can be skipped when turn on "dry_run".
• Support for generating alchemical analysis results in .svg plot.
• Support for including 'cofactors' in the system.

Basic usage:

cd Your_Software_Installation_Directory
git clone https://github.com/freeenergylab/FEP-SPell-ABFE.git

Here, an application example refers to FEP-SPell-ABFE/testing, which can be used to make sure that you can obtain the consistent results with ours (FEP-SPell-ABFE/testing/abfe_testing/results.csv) using this example system under your software environment.

Before launching new ABFE jobs, your working directory should include the following files:

• A proteins directory with structure proteins/[protein_name]/protein.pdb, when "hfe_only=False".
• A ligands directory with structure ligands/[ligand_name]/ligand.sdf(or ligand.mol2).
• A cofactors directory with structure cofactors/[cofactor_name]/cofactor.sdf (or cofactor.mol2), if cofactors are present. [cofactor_name] should be three-capital-letter style, e.g. CFA, CFB et al.
• A ligands.in text file determining which compounds will be submitted to calculate ABFE.
• A config.yaml yaml file. Check out the example file: testing/abfe_testing/config.yaml.
• A sbmitBFE.sh bash file. Check out the example file: testing/abfe_testing/submitBFE.sh.

After the above files are prepared well, please submit your jobs using the following command:

cd Your_Working_Directory
submitBFE.sh -i config.yaml # submitBFE.sh should be modified according to your environment

Advanced usage:

Users can fine-tune the behavior of this workflow by editing the config.yaml file. Please note the comments in the config.yaml file.

Dependencies:

This workflow mainly depends on the packages including Slurm, CUDA, OpenMPI, Amber, Anaconda3 and APBS. With the environment-modules's help, you can use module load command to load the dependent softwares, like:

module purge
module load slurm/slurm/20.02.7
module load cuda12.0/toolkit/12.0.1
module load openmpi/5.0.3
module load anaconda3/FEP-SPell-ABFE
module load amber/amber24_ambertools24
module load apbs/3.4.1

Anaconda3 environment depolyment refers to:

 1. cd Your_Anaconda3_Installation_PATH # e.g. cd $HOME/software/anaconda3/2024.06
 2. wget https://repo.anaconda.com/archive/Anaconda3-2024.06-1-Linux-x86_64.sh
 3. chmod +x Anaconda3-2024.06-1-Linux-x86_64.sh
 4. ./Anaconda3-2024.06-1-Linux-x86_64.sh -u
 5. source $HOME/software/anaconda3/2024.06/bin/activate base
 6. conda create --name FEP-SPell-ABFE --clone base
 7. conda activate FEP-SPell-ABFE
 8. pip install alchemlyb==2.3.1
 9. pip install gridDataFormats==1.0.2
10. pip install loguru==0.7.2
11. pip install mrcfile==1.5.3
12. pip install parmed==4.2.2
13. pip install pymbar==4.0.3
14. pip install rdkit==2024.3.3
 or, you can also create `FEP-SPell-ABFE` environment using `environment_abfe_yml` file, like:
6-14. conda env create --name FEP-SPell-ABFE --file=environment_abfe.yml

###############################################################################

module load anaconda3/FEP-SPell-ABFE

# anaconda3/FEP-SPell-ABFE modulefile, like:
"""
conflict anaconda3

setenv ANACONDA3HOME "$env(HOME)/software/anaconda3/2024.06"
prepend-path PATH "$env(ANACONDA3HOME)/envs/FEP-SPell-ABFE/bin"
prepend-path PYTHONPATH "$env(ANACONDA3HOME)/envs/FEP-SPell-ABFE/lib/python3.12/site-packages"
"""

Amber and AmberTools software installation refers to:

0. module purge
1. module load gcc9/9.3.0
2. module load cuda12.0/toolkit/12.0.1
3. tar xvf Amber24.tar.bz2
4. tar xvf AmberTools24.tar.bz2
5. cd amber24_src
6. cd build
7. vim run_cmake # change to -DMPI=TRUE -DCUDA=TRUE in line 42
8. ./run_cmake
9. make -j32 install # use 32 CPU cores to make

###############################################################################

module load amber/amber24_ambertools24

# amber/amber24_ambertools24 modulefile, like:
"""
conflict amber24

setenv AMBERHOME "$env(HOME)/software/amber/amber24_ambertools24/amber24"

if { [ module-info mode load ] } { puts stdout ". $env(AMBERHOME)/amber.sh" }
"""

APBS software installation refers to:

1. wget https://github.com/Electrostatics/apbs/releases/download/v3.4.1/APBS-3.4.1.Linux.zip
2. unzip APBS-3.4.1.Linux.zip

###############################################################################

module load apbs/3.4.1

# apbs/3.4.1 modulefile, like:
"""
conflict apbs

setenv APBSHOME "$env(HOME)/software/Electrostatics/APBS-3.4.1.Linux"
prepend-path PATH "$env(APBSHOME)/bin"
prepend-path LD_LIBRARY_PATH "$env(APBSHOME)/lib"
"""