One of the common bottlenecks in setting up umbrella sampling simulations is identifying the right set of initial conformations. Whether you’re pulling your molecule manually or trying to distribute configurations along a pathway, getting evenly spaced and representative starting points can be tedious. That’s where the GROMACS Wizard in SAMSON comes in handy.
If you’ve ever found yourself wondering how to select starting structures for umbrella sampling from a trajectory, the GROMACS Wizard streamlines this process with built-in tools that save time and reduce uncertainty. Let’s take a closer look at how to do this directly from a GROMACS trajectory.
Why It Matters
Umbrella sampling hinges on having good coverage of the reaction coordinate space. If you have unevenly spaced or sparse initial conformations, your Potential of Mean Force (PMF) result will suffer. By using an existing trajectory—say, from a center-of-mass (COM) pulling simulation—you can pick frames that are already aligned along your reaction coordinate.
Step-by-Step
Start by switching to the Umbrella Sampling tab in the GROMACS Wizard and selecting your input project. This will automatically find the trajectory file for you.
Next, define the reaction coordinate by selecting two index groups—for example, chain A and chain B—whose center of masses will define the distance you’re analyzing.
You’ll see a plot of the coordinate over time, and SAMSON will suggest initial conformations indicated by dashed lines. Now you can choose how to space your frames. You have two options:
- Set the number of conformations. The tool will distribute them evenly along the reaction coordinate.
- Set a minimum COM spacing. SAMSON will pick frames that are at least this far apart.
Once you’ve selected your spacing criteria, you can also set a start and end frame. Then click on Generate project. This will create a batch project folder that contains a subproject for each conformation and a frames.ndx file indicating which frames were selected.
The advantage? Each subproject is ready for NPT equilibration and subsequent simulation steps, either locally or by submitting them to the cloud.
What to Watch Out For
Make sure your reaction coordinate makes physical sense. If your trajectory doesn’t already follow the expected pathway (e.g., if pulling failed), the sampling windows won’t reflect realistic configurations. A quick check of the coordinate-distance plot can help spot anomalies early.
Conclusion
This trajectory-based setup reduces the guesswork in umbrella sampling. Instead of manually extracting frames or writing scripts, molecular modelers can now focus on fine-tuning parameters and analyzing results—where the real science happens.
To see the full tutorial, diagrams, and steps, visit the official documentation page.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON here.