Assembline

Assembline generates integrative structural models of macromolecular complexes by combining electron microscopy (EM), cross-linking mass spectrometry (XL-MS), and atomic structures or homology models to sample conformational space and satisfy experimental restraints.

Key Features:

• Multi-step protocol: Integrates diverse experimental data across multiple modeling stages to efficiently sample the conformational space of macromolecular complexes, including large and flexible assemblies that are challenging for high-resolution EM.
• Integration with external software: Incorporates the Integrative Modeling Platform (IMP), Python Modeling Interface (PMI), UCSF Chimera, and imp-sampcon to extend modeling, sampling, and analysis capabilities.
• Modeling restraints: Implements novel modeling restraints to increase the accuracy and reliability of generated structural models.
• Efficient sampling and scalability: Enables exhaustive sampling of complexes in the megadalton range, with protocols reported to reach exhaustive sampling within ~100–1,000 CPU-hours.

Scientific Applications:

• Flexible and heterogeneous complexes: Determination of structures for flexible or compositionally heterogeneous macromolecular assemblies.
• In situ and tomographic data integration: Modeling complexes imaged in cellular environments using cryo-electron tomography.
• Integrative structural determination: Combining EM, XL-MS, and atomic structures or homology models to determine architectures not amenable to high-resolution EM alone.

Methodology:

Combines IMP, PMI, UCSF Chimera, and imp-sampcon in a multi-step modeling pipeline that uses proprietary algorithms and novel restraints to build ensembles of models satisfying constraints from EM, XL-MS, and atomic structures or homology models, and provides tools for analysis of those ensembles.