Obtaining a reliable set of initial conformations is a common challenge when setting up umbrella sampling for free energy profile calculations. Whether you’re working with protein-ligand systems or studying molecular interactions along a reaction coordinate, getting this step right is essential to generating meaningful Potential of Mean Force (PMF) results.
The GROMACS Wizard in SAMSON simplifies this process by offering two straightforward approaches for extracting initial conformations. Here’s how each method works and when to choose one over the other.
Option 1: Extract from GROMACS Trajectory
This is the go-to method if you’ve already run a molecular dynamics simulation and have a GROMACS trajectory available. For example, if you’ve previously performed a COM pulling simulation, you can reuse that trajectory to extract meaningful frames.
Once loaded into the GROMACS Wizard, you’ll see a plot of the reaction coordinate distance vs. time. Importantly, suggested frames for initial conformations are marked clearly. You can then choose how conformations are selected:
- By number of conformations – distributes frames evenly along the reaction coordinate.
- By minimum COM spacing – selects frames spaced by at least a specified distance between centers of mass.
Once spacing is defined, you click Generate project. The wizard then creates a batch folder containing subprojects for each selected conformation, ready for NPT equilibration and simulation steps.
Option 2: Use Predefined Conformations or a Path
If you already have a series of conformations—perhaps created with another tool, or manually refined in SAMSON—you can directly use them as starting points. This option also allows more control over what is included and can be useful if your conformations are not part of a continuous trajectory.
In this workflow, follow the Batch computations tutorial through the NVT equilibration step. Then perform NPT equilibration with customized COM pulling parameters, and continue with production simulations as usual.
When to Use Which Method
If you’ve already run a trajectory such as COM pulling and want an automated way to extract initial states: use Option 1.
If you’re picking structures from a different source—a manual selection, docking results, or external software: use Option 2.
These two approaches allow you to flexibly and efficiently set up umbrella sampling projects in SAMSON without needing to script or manually process structures. Whichever route you choose, you’ll soon be ready to move on to equilibration, simulation, and finally WHAM-based PMF analysis.
To learn more and follow the full tutorial, visit the original guide.
SAMSON and all SAMSON Extensions are free for non-commercial use. Get SAMSON here.