Practical overview
When it fits
Use ShEPhERD-2 when a molecular-generation workflow can be guided by 3D interaction features and you need controls such as scaffold constraints, pharmacophore prioritization or combined profiles.
Who it is for
- Researchers exploring generative molecular design from 3D structures or molecular interaction profiles.
- Python users who want command-line or programmatic access to conditioned molecule generation.
- Model developers interested in training or evaluating the model using the repository's scripts and data formats.
Documented uses
- Generate diverse molecular candidates conditioned on a reference structure's shape, electrostatics and pharmacophores.
- Constrain generation around selected scaffold atoms or prioritized pharmacophores.
- Explore molecule-design cases involving bioisosteric fragment merging, dual-target design, selectivity engineering or modality hopping.
- Run model training with the supplied training script and configured HDF5 data.
Requirements & limits
The code is public under the MIT license. The documented setup uses Python 3.11 and xTB; trained model weights are downloaded automatically on first use.
- The repository's suggested environment uses Python 3.11 and a CUDA-specific package extra for GPU installation.
- xTB is a required external dependency and is used for the documented relaxation of SMILES-derived inputs and generated samples.
- SDF input is recommended and preserves supplied poses by default; SMILES inputs are embedded and relaxed.
- The repository documents ARM-specific wheel considerations when selecting CUDA versions above 12.4.
Check current requirements in the official documentation. Source-based guidance does not mean OpenViST has run or independently tested this project.
Generate candidates from a molecular reference
Use the documented command-line inference workflow to generate molecular candidates conditioned on a reference structure or SMILES.
Before you start
- A Linux environment with Python 3.11, as used in the repository's suggested setup.
- The ShEPhERD-2 repository and its Python dependencies installed in a conda environment.
- xTB installed and available on PATH; the repository states it is required and is not pip-installable.
- One input: an SDF structure, SMILES string, SMILES file, or molblock-and-partial-charge pickle.
Steps
Clone the repository and enter its directory.
Create and activate a Python 3.11 conda environment with xTB, then install the project using the documented CUDA-specific package extra.
Run the command below with one supported input option and
--output-dir; the README gives SDF and SMILES examples.python generate.pyReview the generated SDF files under the output directory's
results/reference_NNN/molecules.sdfpath.
Expected outcome
Valid generated molecules are saved as SDF files in the specified output directory's results subfolder.
Guide limitations
- The documented installation example uses a CUDA-specific extra; the README gives separate wheel guidance for ARM systems.
- SMILES inputs are embedded and xTB-relaxed. SDF poses are preserved by default and can optionally be relaxed.
- The repository says trained weights download automatically on first use.
Sources & review
Source record details
- Source availability
- Active
- Sources checked
- 15 October 2026
- Original website title
- coleygroup/shepherd2 · Official homepage title · retained in its source language

