PairMap2 is a web application and Python package for intermediate insertion in relative binding free energy (RBFE/FEP) workflows. Given source and target ligands, it generates intermediate molecules, scores candidate transformations with RDKit and LOMAP, and builds perturbation networks that can be inspected and exported from a browser.

A public instance is available at https://pairmap.yumizsui.com.

PairMap2 prepares intermediate molecules and perturbation networks. It does not run downstream FEP calculations.

• Pair mode for a single source-target transformation from SMILES or SDF input.
• Map mode for a multi-molecule SDF compound series.
• MCS-based edge inspection with common, deleted, and inserted atoms highlighted.
• Browser-based network visualization with Cytoscape.js and molecular rendering with RDKit.js and 3Dmol.js.
• Python API for scripted use.
• Export of generated intermediates and network links for downstream workflows.

• Python 3.12 or later
• A recent web browser for the web UI
• Linux, macOS, or Windows with a working Python environment

Main Python dependencies are listed in pyproject.toml and include RDKit, LOMAP, NetworkX, FastAPI, pandas, NumPy, and Open Babel.

Clone the repository:

git clone https://github.com/ohuelab/PairMap2.git
cd PairMap2

With uv:

uv sync
uv run uvicorn web.backend.main:app --host 127.0.0.1 --port 8000

With pip:

python -m venv .venv
source .venv/bin/activate
python -m pip install -U pip
python -m pip install ./local/gufe_stub -e .
uvicorn web.backend.main:app --host 127.0.0.1 --port 8000

Then open http://127.0.0.1:8000.

Place input molecules in an input directory as SDF files, then run:

from pairmap2 import Pipeline, PipelineConfig

config = PipelineConfig(
    input_dir="./input",
    output_dir="./output",
    save_output=True,
    similarity_threshold=0.6,
    max_path_length=4,
)

result = Pipeline(config).run()
print(result.timings)

When save_output=True, PairMap2 writes:

• intermediate_graph.pkl: graph history and RDKit molecule objects
• intermediate_mols.sdf: source, target, and generated intermediate molecules
• intermediate_links.txt: perturbation-network edges and similarity scores

Common PipelineConfig options include:

If you use the intermediate-insertion method, cite:

@article{Furui2025PairMap,
  author  = {Furui, Kairi and Shimizu, Takafumi and Akiyama, Yutaka and
             Kimura, S Roy and Terada, Yoh and Ohue, Masahito},
  title   = {{PairMap: An intermediate insertion approach for improving the
             accuracy of relative free energy perturbation calculations for
             distant compound transformations}},
  journal = {Journal of Chemical Information and Modeling},
  year    = {2025},
  volume  = {65},
  number  = {2},
  pages   = {705--721},
  doi     = {10.1021/acs.jcim.4c01634}
}

PairMap2 is distributed under the MIT License. See LICENSE for details.