One of the challenges in performing Umbrella Sampling for free energy calculations is obtaining a good set of initial conformations spaced appropriately along a reaction coordinate. Too few or poorly spaced conformations can lead to inaccurate results or wasted computational resources. SAMSON’s GROMACS Wizard offers a dedicated and visual way to generate these conformations whether you already have a trajectory or a predefined path.
The problem with selecting frames manually
When using umbrella sampling, the spacing and number of sampling windows along the reaction coordinate is critical. Typically, molecular modelers would extract conformations manually from longer simulations or trajectories, an error-prone and time-consuming process. By providing both visual and quantitative tools, SAMSON avoids this manual step while giving you full control over the parameters.
Two approaches in SAMSON
You can define your set of initial conformations using SAMSON’s GROMACS Wizard in two main ways:
- From a GROMACS trajectory: Useful when performing umbrella sampling after a pulling simulation like COM pulling.
- From conformations or a path: If you already have a conformational path created within or outside SAMSON.
Using a GROMACS trajectory
In the interface, once you import your trajectory, the reaction coordinate is defined by selecting two atom index groups. SAMSON will then generate a distance vs. time plot, highlighting suggested initial conformations using horizontal and vertical dashed lines. This makes it easy to validate that your conformations are evenly distributed.
How many conformations?
You have two spacing methods to choose from:
- Number of conformations: You define the total number, and SAMSON distributes them equally along the reaction coordinate.
- Minimum COM spacing: Ensures a minimum spacing between consecutive frames based on Center of Mass distance.
Output: a ready-to-run batch
After selecting your conformations, SAMSON generates a batch project folder containing individual project subfolders per conformation and a frames.ndx file that records which frames were chosen. This ensures transparency and reproducibility if you need to regenerate or revisit the exact setups later.
Helpful tips
- Use the option to specify start and end frames to narrow down the sampling window.
- Add custom index groups early on if you need more flexible pulling group definitions later.
In summary, preparing for umbrella sampling becomes less tedious and less error-prone with SAMSON’s visual-driven workflow. It simplifies the step of selecting initial conformations—typically a bottleneck for researchers and students performing free energy calculations.
To learn more about umbrella sampling in SAMSON, head over to the full documentation here.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at https://www.samson-connect.net.