One of the common challenges for molecular modelers performing umbrella sampling is defining the reaction coordinate in a reproducible and visual way. Whether you’re studying ligand unbinding, protein–protein interactions, or mechanical unfolding, the accuracy of your free energy profile depends on how well your reaction coordinate is chosen and prepared.
In this post, we’ll show how you can use the GROMACS Wizard in SAMSON to define reaction coordinates via graphical input and automatically generate a set of initial conformations. The process integrates visualization with data setup, helping you avoid file preprocessing steps and trial-and-error parameter tuning.
Use your trajectory directly
Let’s say you already have a trajectory from a previous simulation—say, a center-of-mass (COM) pulling simulation. You can reuse this trajectory to extract meaningful frames for umbrella sampling. Just open the GROMACS Wizard and switch to the Umbrella Sampling tab.
Once your project is selected, the trajectory is automatically identified. You can now define your reaction coordinate by choosing two index groups. These could be specific atoms or entire chains, for example chain A and chain B.
Visual feedback on your reaction coordinate
After selecting the groups, a plot appears showing the evolution of the distance between them over time. This gives you instant visual feedback and helps in spotting parts of the trajectory that exhibit stable or varying distances. It’s a convenient way to assess where it makes most sense to sample.
Customize the spacing of initial conformations
You can now choose how to select initial conformations along the defined reaction coordinate:
- Number of conformations—frames are spaced evenly along the distance coordinate.
- Minimum COM spacing—frames are selected to ensure a minimum center-of-mass distance between them.
You can also limit the selection to a specific interval of frames, based on time or frame index, which allows you to exclude unstable regions or noise from early simulations.
Structured output ready for batch simulations
Once you’re satisfied with the setup, clicking Generate project produces a batch project folder. This folder contains one simulation project per initial conformation, and an frames.ndx file that tracks which frames were chosen. Everything is structured and timestamped, so you can reload and reproduce the sampling setup later.
This approach reduces manual trajectory slicing, avoids erroneous frame selection, and ensures that your simulations begin from conformations that make sense physically and statistically. It’s a useful shortcut for those working with complex biomolecular systems, where automation and clarity can go a long way.
Ready to streamline the beginning of your umbrella sampling workflow? Learn more in the full documentation.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at https://www.samson-connect.net.