One of the common challenges in setting up Umbrella Sampling simulations is selecting the right initial conformations. For many molecular modelers, this step requires scripting, plotting distances manually, or running external tools—often a time-consuming process. Fortunately, SAMSON’s GROMACS Wizard streamlines this with an intuitive setup process that automates frame selection from a trajectory, making high-quality sampling setups more accessible.
In this post, we’ll walk through how to generate a batch project for Umbrella Sampling directly from an existing GROMACS trajectory, using SAMSON’s visual and user-friendly interface. This process helps you prepare simulations that will later be used to compute the Potential of Mean Force (PMF).
Starting with a GROMACS trajectory
If you already have a trajectory from, for example, a COM pulling simulation, you can use frames from this trajectory as initial conformations. Just switch to the Umbrella Sampling tab in the GROMACS Wizard.
First, choose your input project. The Wizard automatically detects and links the trajectory file associated with your project:
Defining the reaction coordinate
Select two index groups to define your reaction coordinate. This selection determines the collective variable along which the sampling will occur. You’ll see a distance vs time plot with suggested sampling points highlighted, making it easier to visually assess how frames are distributed over time.
Selecting conformations: two approaches
Once the reaction coordinate is visible, you can choose how to space your initial conformations. Here SAMSON offers two intuitive options:
- Number of conformations: The software divides the reaction coordinate evenly into the specified number of segments.
- Minimum COM spacing: Choose a minimum center-of-mass distance between conformations to ensure better sampling resolution.
Generating batch simulation projects
After selecting your spacing method, click Generate project. SAMSON creates a batch project folder, with subfolders for each selected initial conformation. Each subfolder is a ready-to-run simulation project. An frames.ndx file is also generated, summarizing which frames were selected for Umbrella Sampling:
This step drastically reduces the human error and effort normally required to extract multiple conformations across a meaningful reaction coordinate range. It also makes your workflow easily reproducible and structured.
Why this matters
For many researchers performing enhanced sampling simulations, one of the most frustrating bottlenecks is generating a consistent, reproducible subset of starting structures. With SAMSON, this step is not only automated but also made visual, which is particularly advantageous for checking that your reaction coordinate spans the space of interest effectively.
Learn more about Umbrella Sampling in SAMSON and continue with the NPT Equilibration and PMF Analysis steps in the full tutorial here.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at https://www.samson-connect.net.