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Getting Started

Michael R. Shortreed edited this page Jul 19, 2026 · 1 revision

Getting Started

This page gets you from zero to your first in silico digestion in a few minutes. ProteaseGuru is a Windows desktop application.

1. Get ProteaseGuru

Option A — download the app (recommended for most users)

  1. Go to the latest release and download ProteaseGuru.zip.
  2. Unzip it to a folder you can write to (e.g. your Desktop or Documents — not Program Files).
  3. If you downloaded the framework-dependent build, install the free .NET 8 Desktop Runtime first. The self-contained build needs nothing extra.
  4. Double-click ProteaseGuru.exe to launch.

Option B — build from source (for developers)

Requires the .NET 8 SDK and Windows.

git clone https://github.com/smith-chem-wisc/ProteaseGuru.git
cd ProteaseGuru
dotnet build ProteaseGuru.sln -c Release
dotnet run --project ProteaseGuruGui

Or open ProteaseGuru.sln in Visual Studio 2022, set ProteaseGuruGui as the startup project, and press F5.

2. Run your first digestion — 5 steps

  1. Add a protein database. On the Databases Window, click Add (or drag & drop) a UniProt .xml or .fasta file. Compressed .gz files work too. You can add more than one database.
  2. Set your digestion conditions. On the Digestion Conditions Window, select one or more proteases and set your parameters — max missed cleavages, min/max peptide length, and (optionally) a peptide mass range and modifications.
  3. Review and run. The Run Window shows a summary of the databases, proteases, and parameters you chose, plus where your output will be written. Click Run.
  4. Explore your results. When digestion finishes, the Results Summary Window opens. From there you can jump to:
    • Histograms — compare proteases across the whole proteome (peptide length, sequence coverage, unique peptides, and more).
    • Protein Search — look up a specific protein and view its sequence-coverage map, one protease at a time.
  5. Export. Result tables are written automatically to the output folder, and each visualization window can export its own figures — histograms as PDF plus a reproducible .csv, and coverage maps and per-protein results from the Protein Search window.

Requirements at a glance

  • 64-bit Windows (ProteaseGuru is Windows-only at this time).
  • .NET 8 — Desktop Runtime to run a downloaded build, or the SDK to build from source.
  • 8 GB RAM recommended.
  • Input databases in UniProt .xml or .fasta format (.gz accepted).

Need help?

Open an issue or email us at smith_software@chem.wisc.edu.

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