Auto3D 1.13

Generating the Low-energy 3D Conformers from SMILES with Isomer Enumeration and Blitz Geometry Optimization

Auto3D

Introduction

Auto3D automatically find the low-energy structures for the input SMILES. All the processes, like isomer enumeration, duplicate and enantiomer filtering, 3D building, optimization and ranking, are all taken care of by our package. The user can also try out different isomer enumeration engines and optimization engines based on their demands. Auto3D can be run as a Python package or from the terminal command line.

Installatioin

Minimum Dependencies Installatioin

1. Python >= 3.7
2. RDKit (For the isomer engine)
3. OpenBabel >= 3.1.1 (For molecular file processing)
4. PyTorch (For the optimizing engine)

If you have an environment with the above dependencies, Auto3D can be installed by

pip install Auto3D

Otherwise, you can create an environment and install Auto3D. In a terminal, excute the following code will create a environment named auto3D with the minimum dependencies installed, and install Auto3D.

git clone https://github.com/isayevlab/Auto3D_pkg.git
cd Auto3D_pkg
conda env create --file installation.yml --name auto3D
conda activate auto3D
pip install Auto3D

Optional Denpendencies Installation

By installing Auto3D with the above minimum dependencies, you can use Auto3D with RDKit and AIMNET as the isomer engine and optimizing engine, respectively. Two additional optimizing engines are available: ANI-2x and ANI-2xt, which can be installed by (ANI-2xt will be incorporated into the TorchANI package soon):

conda activate auto3D
conda install -c conda-forge torchani

One additional isomer engine is availabel: OpenEye toolkit. It's a commercial software from OpenEye Software. It can be installed by

conda activate auto3D
conda install -c openeye openeye-toolkits

To calculate thermodynamical properties (such as Gibbs free energy, enthalpy, entropy, geometry optimization) with Auto3D, ASE needs to be installed:

conda activate auto3D
conda install -c conda-forge ase

Basic Usage

A .smi file that stores your chemical structures is needed as the input for the package. You can find an example input files in the examples/files folder. Basically, an .smi file contains SMILES and their IDs. ID can contain anything like numbers or letters, but not "_", the underscore. You can import Auto3D as a library in any Python script, or run Auto3D through the commalnd line interface (CLI). They are equivalent in findig the low-energy 3D conformers.

Using Auto3D as a Python library

The following script will give you the 3-dimensional structures, which are stored in a file that has the same name as your input file, but is appended with _3d.sdf.

from Auto3D.auto3D import options, main

if __name__ == "__main__":
    path = "example/files/smiles.smi"
    args = options(path, k=1)   #args specify the parameters for Auto3D 
    out = main(args)            #main accepts the parameters and run Auto3D

Using Auto3D in a terminal command line

Alternatively, you can run Auto3D through CLI.

cd <replace with your path_folder_with_auto3D.py>
python auto3D.py "example/files/smiles.smi" --k=1

The parameter can be provided via a yaml file (for example parameters.yaml). So the above example is equivalent to

cd <replace with your path_folder_with_auto3D.py>
python auto3D.py parameters.yaml

The 3 examples will do the same thing: Both run Auto3D and keeps 1 lowest-energy structure for each SMILES in the input file. It uses RDKit as the isomer engine and AIMNET as the optimizng engine by default. If you want to keep n structures for each SMILES, simply set k=n or --k=n. You can also keep structures that are within x kcal/mol from the lowest-energy structure for each SMILES if you replace k=1 with window=x.

When the running process finishes, there will be folder with the name of year-date-time. In the folder, you can find an SDF file containing the optimized low-energy 3D structures for the input SMILES. There is also a log file that records the input parameters for Auto3D and some running meta data.

Wrapper functions

Auto3D also provides some wrapper functions for single point energy calculation, geometry optimization and thermodynamic analysis. Please see the example folder for details.

Parameters in Auto3D

For Auto3D, the Python package and CLI share the same set of parameters. Please note that -- is only required for CLI. For example, to use ANI2x as the optimizing engine, you will use

from Auto3D.auto3D import options, main

if __name__ == "__main__":
    path = "example/files/smiles.smi"
    args = options(path, k=1, optimizing_engine="ANI2x")  
    out = main(args)           

if you use the Python script; You will use

cd <replace with your path_folder_with_Auto3D_pkg>
python auto3D.py "example/files/smiles.smi" --k=1 --optimizing_engine="ANI2x"

if you use the CLI.

State	Type	Name	Explanation
	required argument	path	a path of .smi file to store all SMILES and IDs
ranking	required argument	--k	Outputs the top-k structures for each SMILES. Only one of --k and --window need to be specified.
ranking	required argument	--window	Outputs the structures whose energies are within a window (Hatree) from the lowest energy. Only one of --k and --window need to be specified.
job segmentation	optioinal argument	--memory	The RAM size assigned to Auto3D (unit GB). By default None, and Auto3D can automatically detect the RAM size in the system.
job segmentation	optional argument	--capacity	By default, 40. This is the number of SMILES that each 1 GB of memory can handle.
isomer enumeration	optional argument	--enumerate_tautomer	By default, False. When True, enumerate tautomers for the input
isomer enumeration	optional argument	--tauto_engine	By default, rdkit. Programs to enumerate tautomers, either 'rdkit' or 'oechem'. This argument only works when --enumerate_tautomer=True
isomer enumeration	optional argument	--isomer_engine	By default, rdkit. The program for generating 3D conformers for each SMILES. This parameter is either rdkit or omega. RDKit is free for everyone, while Omega reuqires a license.))
isomer enumeration	optional argument	--max_confs	Maximum number of conformers for each configuration of the SMILES. The default number depends on the isomer engine: up to 1000 conformers will be generated for each SMILES if isomer engine is omega; The number of conformers for each SMILES is the number of heavey atoms in the SMILES minus 1 if isomer engine is rdkit.
isomer enumeration	optional argument	--enumerate_isomer	By default, False. When True, unspecified cis/trans and r/s centers are enumerated
isomer enumeration	optional argument	--mode_oe	By default, classic. The mode that omega program will take. It can be either 'classic' or 'macrocycle'. Only works when --isomer_engine=omega
isomer enumeration	optional argument	--mpi_np	By default, 4. The number of CPU cores for the isomer generation step.
optimization	optional argument	--optimizing_engine	By default, AIMNET. Choose either 'ANI2x', 'ANI2xt', or 'AIMNET' for energy calculation and geometry optimization.
optimization	optional argument	--use_gpu	By deafult, True. If True, the program will use GPU
optimization	optional argument	--gpu_idx	By defalt, 0. It's the GPU index. It only works when --use_gpu=True
optimization	optional argument	--opt_steps	By deafult, 5000. Maximum optimization steps for each structure
optimization	optional argument	--convergence_threshold	By deafult, 0.003 eV/Å. Optimization is considered as converged if maximum force is below this threshold
optimization	optional argument	--patience	If the force does not decrease for a continuous patience steps, the conformer will drop out of the optimization loop. By default, patience=1000
duplicate removing	optional argument	--threshold	By default, 0.3. If the RMSD between two conformers are within the threhold, they are considered as duplicates. One of them will be removed. Duplicate removing are excuted after conformer enumeration and geometry optimization
housekeeping	optional argument	--verbose	By default, False. When True, save all meta data while running
housekeeping	optional argument	--job_name	A folder that stores all the results. By default, the name is the current date and time

Citation:

https://doi.org/10.26434/chemrxiv-2022-fw3tg