Ensembler

Ensembler automates preparation of simulation-ready protein structures and generates ensembles for high-throughput molecular simulations across protein superfamilies.

Key Features:

• Scalability: Handles input ranges from individual proteins to entire superfamilies for large-scale model preparation.
• Comparative Modeling with PDB Templates: Uses Protein Data Bank (PDB) structures as templates and accommodates multiple conformational states.
• Loop Reconstruction and Atom Addition: Reconstructs missing loops and adds missing atoms to produce complete protein models.
• Structure Culling: Removes nearly identical structures to ensure ensemble diversity.
• Protonation State Assignment: Assigns appropriate protonation states for residues to support accurate simulations.
• Solvation and Refinement: Solvates models in explicit solvent and refines them using molecular simulation techniques.
• Output Ensemble Generation: Produces ensembles of refined, simulation-ready structures for execution on computer clusters, supercomputers, or distributed platforms such as Folding@home.
• Facilitation of Kinetic Modeling: Provides diverse initial configurations to aid construction of kinetic models, including Markov state models (MSMs).

Scientific Applications:

• Superfamily-scale protein dynamics: Enables study of conformational dynamics and structural variation across entire protein superfamilies using homologous structural data.
• Kinase catalytic-domain modeling: Demonstrated to construct models for all catalytic domains in the human tyrosine kinase family using kinase structures from multiple organisms as templates.

Methodology:

Comparative modeling using PDB templates; loop reconstruction and atom addition; structure culling; protonation state assignment; solvation in explicit solvent; and refinement using molecular simulation techniques, including molecular dynamics simulations.