ModelX

ModelX predicts RNA-protein interactions and enables sequence-level reengineering of RNA-protein interfaces for biomolecular modeling and analysis.

Key Features:

• RnaX integration: Integrates RnaX, a fragment pair-based method, for predicting RNA-binding sites on target proteins.
• Fragment database: Constructs an exhaustive database of reusable structural motifs and fragment pairs from previously resolved RNA-protein complexes.
• Fragment-based docking: Performs efficient docking by placing fragment pairs onto protein structures to explore backbone-compatible interactions.
• Statistical forcefield: Applies a statistical forcefield to rapidly distinguish true backbone-compatible interactions from incompatible placements.
• FoldX integration: Integrates the FoldX protein design forcefield to perform sequence-specific reengineering of RNA-protein interfaces.
• Conformational mutagenesis modeling: Mimics conformational changes observed in protein and RNA mutagenesis to modify and evaluate interfaces.
• Computational efficiency: Reduces computational cost relative to traditional conformational dynamics simulations.

Scientific Applications:

• Interface prediction: Predicts RNA-binding sites and RNA-protein interfaces relevant to transcription regulation, splicing, translation, and gene silencing.
• Rational interface design: Enables rational design and sequence-level engineering of RNA-protein interfaces for therapeutic development and molecular biology research.
• Mutagenesis analysis: Assesses the structural and sequence effects of protein and RNA mutagenesis on interface compatibility.

Methodology:

Integration of the RnaX fragment pair-based method; construction of a fragment-pair database from resolved RNA-protein complexes; fragment-based docking onto protein structures; application of a statistical forcefield to filter backbone-compatible interactions; and use of FoldX for sequence-specific reengineering while modeling conformational changes observed in protein and RNA mutagenesis.