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Conformational Density

RECOVAR can estimate the probability density of conformations in the latent space. This enables:

  • Free energy estimation (free energy = -kT ln(density))
  • Identification of stable conformational states
  • High-density trajectory computation

Worked example

The Tutorial demonstrates conformational density estimation on EMPIAR-10180 (spliceosome), including trajectory computation through the density landscape.

Estimating density

recovar estimate_conformational_density output --pca_dim=4 --z_dim_used=4

This deconvolves the particle distribution in latent space to produce density estimates at multiple regularization levels. The output includes a recommended "knee" regularization (deconv_density_knee.pkl) that balances noise suppression with resolution.

Flag Default Description
--pca_dim 4 PCA dimensions for density estimation
--z_dim_used Auto Latent dimension to use
--percentile_reject 10 Reject % of data with large covariance

Note

Runtime scales exponentially with --pca_dim. Keep it at 4 or below.

Estimating stable states

recovar estimate_stable_states density_output/data/deconv_density_knee.pkl \
    -o stable_states

Identifies local minima in the free energy landscape. The first argument is the density .pkl file produced by estimate_conformational_density.

Using density for trajectories

The density can guide trajectory computation to follow low free-energy paths:

recovar compute_trajectory output -o trajectory --zdim=10 \
    --density density_output/data/deconv_density_knee.pkl \
    --endpts centers.txt --ind 0,1

Without --density, trajectories follow straight lines in latent space. With density, they curve to follow high-density (low free-energy) regions.

GUI alternative

In the GUI's latent space explorer, you can select two points on the scatter plot to compute a trajectory interactively. See the GUI Guide.

Using the GUI

In the web GUI (recovar gui), click + New Job and select Density Estimation from the Job Type dropdown. Set the result directory (path to pipeline output), PCA dimension, and latent dimension, then submit.

You can also reach density estimation from a completed pipeline job's Suggested Next Steps by clicking Estimate conformational density, which pre-fills the result directory.

After density estimation completes, use the Latent Space Explorer to color particles by conformational density and visually identify stable states.