Umbrella Sampling is a key technique for estimating free energy profiles along a reaction coordinate. However, a common frustration for molecular modelers using GROMACS is setting up all the simulations required to populate the reaction coordinate. Selecting the right conformations, preparing input files, defining pull parameters—it’s easy to get overwhelmed.
If you’ve ever struggled to generate consistent and efficient Umbrella Sampling setups, the GROMACS Wizard in SAMSON can help streamline the process. In this blog post, we’ll walk through setting up a complete Umbrella Sampling project in just a few steps—starting from a GROMACS trajectory.
Why starting from a trajectory can save you time
Many users already have simulation data, for instance from a Center of Mass (COM) pulling simulation. SAMSON lets you reuse this data to generate a full Umbrella Sampling project, avoiding repetitive file preparation and reducing setup errors.
Step-by-step: Generate an Umbrella Sampling Project
After importing your trajectory into SAMSON, head to the Umbrella Sampling tab of the GROMACS Wizard. Choose your input project—SAMSON identifies the trajectory automatically.
Next, define the reaction coordinate you want to study by selecting two index groups (e.g., two chains or molecular fragments). You can also create custom index groups if needed for your analysis.
SAMSON automatically visualizes the reaction coordinate: a distance vs. time plot shows where candidate conformations for sampling are located. Then, choose your spacing strategy for initial conformations:
- By number: Specify how many evenly distributed conformations SAMSON should pick.
- By COM spacing: Define a minimum center-of-mass distance between frames.
You can also control the time window by setting start and end frames for sampling.
When you’re ready, click Generate project. SAMSON creates a batch project folder (timestamp_umbrella) containing simulation-ready subprojects for each selected conformation. You’ll also get a frames.ndx file with detailed information about which trajectory frames were selected.
More flexibility, fewer errors
This feature addresses a frequent source of error in umbrella sampling: choosing representative structures manually, inconsistently, or sparsely. SAMSON provides a clear, visual, and efficient way to select and organize data. It also reduces the odds of file mismatches, naming issues, and parameter misalignment that often creep into manual workflows.
Automate and move on
Once your batch project is created, you’re ready to run NPT equilibration, production MD, and eventually PMF analysis. Whether you compute locally or push to the cloud, you’re always working with a structured, reproducible setup.
For a complete guide, refer to the official documentation: Umbrella Sampling in GROMACS Wizard
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at https://www.samson-connect.net.