MorphOT: transport-based interpolation between EM maps with UCSF ChimeraX.

Area of Science:

• Structural Biology
• Biophysics

Background:

• Cryogenic electron microscopy (cryo-EM) enables the study of molecular structures.
• Capturing conformational heterogeneity is crucial for understanding protein dynamics.
• Existing methods struggle to accurately represent transitions between different molecular states.

Purpose of the Study:

• To develop a novel method for visualizing conformational heterogeneity in cryo-EM data.
• To generate realistic morphing trajectories between different 3D electron microscopy (EM) maps.
• To better understand the implications of conformational flexibility in biological molecules.

Main Methods:

• Utilized an optimal-transport-based metric to interpolate between EM maps.
• Developed a method to produce continuous morphing trajectories, displacing densities rather than blending them.
• Implemented the method as a ChimeraX plug-in (MorphOT) for user accessibility.

Main Results:

• Demonstrated that the optimal-transport method generates realistic transitions between EM maps.
• Showcased the ability to produce continuous morphing trajectories that accurately represent conformational changes.
• The developed MorphOT tool effectively visualizes molecular dynamics captured by cryo-EM.

Conclusions:

• Optimal transport provides a robust framework for analyzing conformational heterogeneity in cryo-EM.
• The MorphOT tool facilitates the visualization and interpretation of dynamic molecular processes.
• This approach enhances the understanding of protein function through the analysis of conformational landscapes.