HEMNMA-3D

HEMNMA-3D analyzes continuous conformational variability of macromolecular complexes from cryo-electron tomography subtomograms to characterize native-state structural dynamics.

Key Features:

• Continuous Conformational Analysis: Analyzes continuous conformational changes in cryo-electron subtomograms of macromolecular complexes in their native cellular context.
• Elastic and Rigid-body 3D-to-3D Iterative Alignments: Performs elastic matching using molecular mechanics simulations (Normal Mode Analysis) combined with rigid-body 3D-to-3D iterative alignments to recover conformation, orientation, and position while compensating for the missing wedge from limited tilt angles.
• Visualization of Conformational Dynamics: Projects alignment-derived conformational parameters into reduced-dimensional spaces (typically 2D or 3D) to visualize conformational distributions and trajectories and to compute 3D averages and movies along selected trajectories.
• Validation and Application: Validated on synthetic datasets and applied to experimental cryo-ET subtomograms, including analysis of in situ nucleosome conformational variability.

Scientific Applications:

• Structural Biology: Maps continuous conformational landscapes of proteins and macromolecular complexes from cryo-ET subtomograms.
• Cell Biology: Investigates dynamics of macromolecular complexes within crowded cellular environments using subtomogram analysis.
• Nucleosome Dynamics: Analyzes in situ nucleosome conformational variability from cryo-ET data.

Methodology:

Elastic matching via molecular mechanics simulations (Normal Mode Analysis), rigid-body 3D-to-3D iterative alignments, compensation for the missing wedge from limited tilt angles, projection of conformational parameters into reduced-dimensional spaces (2D/3D), and computation of 3D averages and movies along selected trajectories.