From Trajectory to Insight: Preparing Initial Conformations for Umbrella Sampling in SAMSON

For molecular modelers seeking accurate free energy landscapes, Umbrella Sampling remains an essential technique. But before you can compute the Potential of Mean Force (PMF), the often overlooked bottleneck lies in one critical step: selecting meaningful initial conformations from your simulation trajectory. This step is not only crucial for the scientific validity of your results—it can also be rather… tedious.

Thankfully, if you’re using GROMACS Wizard in SAMSON, this process is thoughtfully assisted, guiding you through decisions that would otherwise require scripting, plotting, and repeated trial-and-error.

Using a GROMACS Trajectory as Your Starting Point

Let’s say you’ve just completed a simulation—such as a center of mass (COM) pulling run—and now you’re ready to move on to Umbrella Sampling. The GROMACS Wizard in SAMSON allows you to efficiently extract initial conformations directly from your existing GROMACS trajectory.

Here’s how:

  1. Switch to the Umbrella Sampling tab in GROMACS Wizard.
  2. Select your input project, which automatically links your trajectory from the project folder.

Input for Umbrella Sampling

Defining the Reaction Coordinate

A clear reaction coordinate is the backbone of Umbrella Sampling. Using the interface, you can specify two index groups within your molecular system—e.g., chain A and chain B—and GROMACS Wizard visualizes the distance over time. Vertical dashes indicate suggestions for initial conformations.

Choose the reaction coordinate

You can define your spacing strategy based on:

  • Number of Conformations: Select how many you want, and the software will space them evenly along the reaction coordinate.
  • Minimum COM Spacing: Define desired spatial separation for robust sampling.

Choose the conformations based on the total number of conformations

Choose the conformations based on the COM spacing

You can also refine your selection window by choosing specific start and end frames. This is useful if you know certain regions better represent the equilibrium part of your trajectory.

One Click to Batch Creation

Once you’re happy with the conformations and spacing, just click Generate project. This builds a batch project structure with individual subfolders—one per conformation. The .ndx file tracks these frames so you won’t lose track of where each came from.

A folder with output

With all initial conformations prepared, you’re set to continue with equilibration and simulation, advancing your Umbrella Sampling workflow smoothly and reproducibly.

This approach significantly reduces overhead in setting up sampling windows and avoids drift-prone manual selection. Ultimately, this not only increases reproducibility but also encourages more nuanced and exploratory usage of Umbrella Sampling in your molecular projects.

To learn more, read the full Umbrella Sampling tutorial in the SAMSON documentation.

SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at https://www.samson-connect.net.

Comments are closed.