Running umbrella sampling simulations in molecular modeling can be complex, especially when dealing with dozens of starting conformations and ensuring consistency across multiple simulations. One challenge that many molecular modelers face is setting up those initial conformations and defining simulation parameters in a reproducible, semi-automated way. If you’ve ever wished there was a faster, less error-prone approach to streamline this part of your workflow, then this article is for you.
The GROMACS Wizard extension in SAMSON provides a well-integrated way to define and launch umbrella sampling simulations from either GROMACS trajectories or path-based conformations. In this post, we’ll focus on setting up umbrella sampling projects from GROMACS trajectories.
From Trajectory to Batched Simulation
If you’ve already run a center-of-mass (COM) pulling simulation or another form of trajectory in GROMACS, you can reuse it to define starting conformations across a reaction coordinate. Simply open the GROMACS Wizard in SAMSON and switch to the Umbrella Sampling tab. There, you’ll choose your previous project as input, and the trajectory file will be detected automatically.
Next, you define a reaction coordinate by selecting two index groups (e.g., “chain A” and “chain B”) between which the sampling will be performed. You can also define custom index groups for finer control through a separate preparation step if needed.
Control Over Initial Conformations
Once the reaction coordinate is defined, the Wizard constructs a distance vs. time plot along that coordinate, allowing you to visualize and interactively select starting conformations.
The most useful part? You can choose how to sample those conformations using two different strategies:
- Total number of conformations – equally spaced across the reaction coordinate
- Minimum COM spacing – selected based on a minimum distance between structures
After defining your setup, clicking “Generate project” creates a batch project containing subfolders for each starting conformation. These batch folders are named with timestamps and contain all necessary files (like frames.ndx) for tracing which frames were selected.
Why It Helps
This setup phase is where mistakes in index groups, trajectory slicing, or parameter definitions can derail your simulations. By automating this process through GROMACS Wizard, fewer manual steps are required, and the resulting batch project is neatly organized for subsequent equilibration and MD runs.
Umbrella sampling is widely used for Potential of Mean Force (PMF) calculations, and the initial preparation work can determine the reliability of the results. This user-friendly project generation process ensures more reproducible sampling while saving time and reducing potential errors.
If you’re ready to explore batch-based umbrella sampling setups, check out the full documentation: https://documentation.samson-connect.net/tutorials/gromacs-wizard/umbrella-sampling/
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON here.