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Getting Started
Michael R. Shortreed edited this page Jul 19, 2026
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This page gets you from zero to your first in silico digestion in a few minutes. ProteaseGuru is a Windows desktop application.
Option A — download the app (recommended for most users)
- Go to the latest release and download
ProteaseGuru.zip. - Unzip it to a folder you can write to (e.g. your Desktop or Documents — not
Program Files). - If you downloaded the framework-dependent build, install the free .NET 8 Desktop Runtime first. The self-contained build needs nothing extra.
- Double-click
ProteaseGuru.exeto 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.
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Add a protein database. On the Databases Window, click Add (or drag & drop) a UniProt
.xmlor.fastafile. Compressed.gzfiles work too. You can add more than one database. - 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.
- 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.
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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.
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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.
- 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
.xmlor.fastaformat (.gzaccepted).
Open an issue or email us at smith_software@chem.wisc.edu.