Molecular modelers using umbrella sampling often face a common challenge: selecting meaningful and well-distributed initial conformations. Poor choices at this early stage can lead to inefficient sampling or misleading Potential of Mean Force (PMF) results. Fortunately, the GROMACS Wizard in SAMSON provides a straightforward way to automate this step and visualize your choices along a reaction coordinate — without writing a single line of code.
Let’s focus on one specific workflow: extracting initial conformations from a GROMACS trajectory.
Visualizing and Selecting Conformations
After switching to the Umbrella Sampling tab in the GROMACS Wizard, you can select your previously generated project as input. The wizard will automatically identify the trajectory file, removing guesswork and manual browsing.
Next, you specify the reaction coordinate by selecting two index groups. These groups define the molecular components whose distance you’ll monitor. You also have the option to define custom index groups, which can be reused later during analysis or simulation — particularly useful when working with non-standard molecular partitions.
Spacing Options for Conformations
Once your coordinate is defined, a reaction coordinate plot is automatically displayed. This plot shows how the distance evolved during the simulation and marks suggested conformations as vertical dashed lines. It lets you gauge whether certain distances are oversampled or underrepresented.
To finalize your selection, you can choose how the conformations should be spaced:
- Number of conformations: Useful if you want a fixed number of samples that span the distance evenly.
- Minimum COM spacing: Ensures that conformations are spaced at least a specific distance apart (based on center of mass), which is useful for avoiding overlap and ensuring sampling diversity.
Additionally, you may restrict the conformations to a known relevant time window by specifying the range of frames to consider.
Organizing the Output
When you click Generate project, SAMSON automatically creates a batch project. This includes subfolders for each selected conformation and a frames.ndx file that records the frame numbers used. This makes it seamless to run simulations in parallel locally or in the cloud, with each window simulation having its own well-prepared folder.
Final Thoughts
If you’ve ever manually written scripts to extract relevant frames or struggled with comparing PMF results due to inconsistent spacing, this workflow can improve both reliability and efficiency. Most importantly, it lets you keep your focus on interpreting results rather than setting up simulations.
Want a deep dive into the whole umbrella sampling pipeline? You can learn more by reading the full tutorial here.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON at https://www.samson-connect.net.