One of the most common frustrations for molecular modelers running umbrella sampling simulations is deciding on the best way to choose initial conformations. Too sparse, and you lose resolution. Too dense, and computational costs skyrocket. Luckily, the GROMACS Wizard in SAMSON makes this process visual, flexible, and (more importantly) reproducible.
In umbrella sampling, choosing frames along a reaction coordinate is critical for constructing a meaningful Potential of Mean Force (PMF) profile. GROMACS Wizard offers a visual way to extract initial conformations from GROMACS trajectories, making it easier to set up meaningful batches for simulation. Here’s a look at how to do that, and why it helps reduce uncertainty in your simulation setup.
Start with a Trajectory
If you already have a GROMACS trajectory—perhaps obtained from a center-of-mass (COM) pulling simulation—you can use it directly. The GROMACS Wizard will automatically detect it when you switch to the Umbrella Sampling tab and hit “Choose input project”:
Define Your Reaction Coordinate
The next step is specifying the reaction coordinate: select two index groups, such as two molecular chains. You can also create custom index groups within the wizard, giving you the flexibility to tailor the reaction coordinate to your system of interest:
Visualize and Choose Initial Conformations
Once your reaction coordinate is selected, a plot will display the distance vs time profile from your trajectory, including suggestions for initial conformations (vertical and horizontal dashed lines). This visualization is extremely useful as it provides an intuitive way to select frames:
- By number: specify how many conformations you wish to extract, evenly spaced along the reaction coordinate.
- By spacing: specify the minimum COM distance between conformations to capture structural diversity.
Batch Project Output
Once you’re satisfied with your selection, click Generate project. This will create a batch project folder that contains one subfolder for each selected frame (i.e., each initial conformation). The frames.ndx file will document which frames were included, making your simulation setup traceable.
Why This Matters
Manual selection of initial conformations is common practice, but it’s time-consuming and open to bias. With the GROMACS Wizard’s visual tools, you gain better control over how your sampling space is constructed, which reduces errors and helps with reproducibility—a key concern for computational modeling workflows.
To learn more about how to perform umbrella sampling using GROMACS Wizard, including PMF analysis and NPT equilibration, visit the full tutorial at https://documentation.samson-connect.net/tutorials/gromacs-wizard/umbrella-sampling/.
Please note: SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON from https://www.samson-connect.net.