One of the common challenges in setting up umbrella sampling simulations is preparing a good set of initial conformations. Molecular modelers often struggle to extract regular conformations from trajectories or paths, identify reaction coordinates properly, and automate the setup process across multiple simulations. If you’ve felt overwhelmed trying to prepare such simulations manually, here’s a streamlined approach that could significantly reduce setup time and avoid common pitfalls.
SAMSON’s GROMACS Wizard provides a reliable and intuitive way to generate structured umbrella sampling projects. In this post, we’ll focus specifically on how to select initial conformations using a trajectory you already have – typically from a COM pulling simulation. This sets up your simulations for smooth progression through equilibration, production, and PMF analysis.
Why It Matters
Badly spaced or inconsistent initial conformations can lead to uneven sampling along your reaction coordinate and complicate subsequent PMF calculations. A solid set of well-spaced conformations makes everything downstream more reliable and efficient, especially when you plan to use methods like WHAM for analysis.
Start With a GROMACS Trajectory
If you already have a GROMACS trajectory, for example from a previous COM pulling simulation, you can directly use it as the basis for selecting your initial conformations. After switching to the Umbrella Sampling tab in the GROMACS Wizard, select your input project. The Wizard scans the folder and automatically finds your trajectory file.
Define the Reaction Coordinate
Next, specify your reaction coordinate by selecting two index groups—these typically represent the molecular fragments whose distance you want to analyze. You can also add custom index groups during this step.
Preview and Select Your Spacing
The tool visualizes the distance along the reaction coordinate across the trajectory over time. Vertical and horizontal dashed lines suggest potential initial conformations automatically based on your input.
From here, you can choose to define conformations based on:
- Number of conformations: Uniformly distributes conformations between start and end points of the trajectory.
- Minimum COM spacing: Only selects conformations that meet a spacing threshold between centers of mass.
Generate Your Batch Project
Once you’ve settled on your spacing, click Generate project. A new batch project folder is created, with timestamped subfolders for each conformation. Each folder contains its own simulation input files, ready for equilibration or production runs. The tool also generates a frames.ndx file documenting which trajectory frames were selected.
What You Gain
Instead of manually extracting and validating conformations frame-by-frame, the GROMACS Wizard builds a reliable batch project structure with a few clicks. This ensures consistency and provides a clean path toward NPT equilibration and PMF analysis. The visualization tools also reduce ambiguity when deciding which regions of the trajectory yield the best snapshots.
Want to explore further? You can read the full documentation page here:
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 at https://www.samson-connect.net.