GRASP Library Designer

Codon-optimize GRASP (Farley et al., NAR 2025) binder DNA for Golden Gate assembly.

PyPI: grasp-library-designer · Import: grasp_library

Open in Google Colab

Click a badge → run 0 · Install (PyPI) → fill the forms top to bottom. No GitHub token needed.

Notebook	Open
One-shot (one RNA → configured Level −1 order fragments)
Library (42-module redesign → GAP compile)

Direct links:

• One-shot: https://colab.research.google.com/github/JustABiologist/grasp-library-designer/blob/main/grasp_oneshot_designer.ipynb
• Library: https://colab.research.google.com/github/JustABiologist/grasp-library-designer/blob/main/grasp_library_designer.ipynb

Each notebook installs with:

%pip install -q -U "grasp-library-designer>=0.1.8"

Bundled GenBank modules, Potapov ligase-only matrices, and Pryor Golden Gate cycling matrices ship inside the package (materialize_project()).

Install locally

pip install grasp-library-designer
# optional notebook extras
pip install "grasp-library-designer[notebook]"

from grasp_library import materialize_project, build_default_config, LigationFidelityCalculator

project = materialize_project()  # ./grasp_library_project + GenBank
config = build_default_config(project / "input")
print(LigationFidelityCalculator(25, 18).set_fidelity(["AATG", "GATA"]))

From a blank Colab / Jupyter, you can also drop the Forms notebooks onto disk:

%pip install -q -U grasp-library-designer
from grasp_library import write_notebook
write_notebook("oneshot")   # or "library"
# then open the written .ipynb from the file browser

What each notebook does

Hard constraints (library path): the protein sequence is fixed and every movable four-base cut is restricted to the invariant ARELF motif. The search explores all motif-relative offsets 0–11 rather than only the four cut positions chosen in the paper. A candidate is therefore an (overhang, ARELF offset) pair, and each part is rematerialized before codon optimization. Objectives are ligation fidelity, codon optimality, and synthesis fitness.

Ligation fidelity is reported per physical six-overhang Level 0 reaction (and optionally as an explicitly labelled product across independently transformed blocks). The scalar is the orientation-invariant geometric mean of the two directional products. The dashboard includes directly measured Pryor et al. 37↔16 °C Golden Gate cycling matrices as labelled GRASP proxies. Potapov’s ligase-only data contain no 16 °C matrix, so the program does not interpolate or blend static temperature matrices. These scores are optimization surrogates, not cloning guarantees. Synthesis QC distinguishes PASS, WARNING, and FAIL; vendor profiles remain transparent heuristics with vendor_acceptance_confirmed=False.

The order file contains double-stranded synthesis fragments with paired, inward-facing BsaI sites. Every interface is explicit in CONFIG and editable in the dashboard. Terminal-side labels name the physical end of the coding- oriented construct: N-terminal side = 5′ end and C-terminal side = 3′ end. Every overhang label is written 5′→3′, so compatible ends are reverse complements. Bases retained on the assembled coding strand are tracked separately where they differ from the physical sticky-end label. Defaults are:

• Level −1 entry vector: 5′/N side AACA, 3′/C side GGAG.
• Level 0 acceptor release boundaries: 5′/N side CTCA, 3′/C side CGAG.
• CDS1 3′/C side / CDS2 5′/N side: CTTC / GAAG.
• Resulting Level 1 cassette: 5′/N side GCCC, 3′/C side GCGA.

The first and last pairs are custom defaults. They must not be described as native pAGM1311 or pICH47802 interfaces. A deposited-GRASP preset is retained for pAGM1311/pAGM9121 compatibility. When no acceptor-vector sequence is provided, the exporter validates the insert geometry and interface requirements but honestly reports that it did not simulate the vector backbone.

The exported GRASP tract is a PPR block set, not a standalone expression plasmid. The PPR block-chain check does not validate an entire Level 1 expression construct; promoter, N-terminal domain, effector, terminator, and acceptor context must be supplied separately.

For 14S and 19S, the intermediate directional pairs are also configurable: GTGA/TCAC for the CDS1 3′/C-side → CDS14 5′/N-side junction and CACG/CGTG for the CDS14 3′/C-side → CDS19 5′/N-side junction. Default ARELF offsets are 4 and 1; the CDS1→CDS2 default offset is 11.

Develop from source

git clone https://github.com/JustABiologist/grasp-library-designer.git
cd grasp-library-designer
python3 -m venv .venv
source .venv/bin/activate
pip install -e ".[notebook,dev]"

Package layout

grasp_library/                 # installable Python package
  data/profiles/.../genbank/   # bundled GRASP GenBank modules
  notebooks/                   # Colab Forms notebooks (also at repo root)
  paths.py                     # materialize_project()
  ...
third_party/dawdlib_golden_gate/   # Potapov ligation fidelity (AGPL)

License

AGPL-3.0 (required by the vendored GGAssembler / dawdlib ligation engine). See LICENSE and THIRD_PARTY_LICENSES.md.

GRASP sequences: Farley et al., Nucleic Acids Res. 2025.