beita6969 When to Trigger
Activate this skill when the user mentions:
- Protein folding, AlphaFold, ESMFold, RoseTTAFold
- PDB files, structural analysis, Ramachandran plots
- Molecular docking, binding affinity, binding pockets
- Homology modeling, threading, ab initio structure prediction
- Protein-protein interactions (PPI), interface analysis
- Structural alignment, RMSD, TM-score
- Cryo-EM, X-ray crystallography data interpretation
Step-by-Step Methodology
- Retrieve or predict structure - Search PDB for experimental structures (by UniProt ID or gene name). If unavailable, use AlphaFold DB or run ESMFold. Check pLDDT confidence scores for predicted structures.
- Quality assessment - For experimental structures: check resolution, R-free, and completeness. For predictions: evaluate pLDDT per-residue and PAE (predicted aligned error) matrices.
- Structural analysis - Identify secondary structure elements (helices, sheets, loops). Compute solvent-accessible surface area. Map conserved residues and functional domains.
- Binding site identification - Use fpocket, SiteMap, or DoGSiteScorer for pocket detection. Cross-reference with known ligand binding from PDBe or BindingDB.
- Molecular docking - Recommend AutoDock Vina, GNINA, or Glide. Define grid box around binding site. Report binding energy (kcal/mol) and key interactions (H-bonds, hydrophobic, pi-stacking).
- Structural comparison - Align structures using TM-align or FATCAT. Report RMSD and TM-score. Identify conformational changes between states.
- Visualization guidance - Recommend PyMOL, ChimeraX, or Mol* for rendering. Specify coloring schemes (by chain, B-factor, electrostatics, or conservation).
Key Databases and Tools
- PDB / PDBe - Experimental protein structures
- AlphaFold DB - AI-predicted structures for UniProt entries
- UniProt - Protein sequences, domains, and annotations
- InterPro / Pfam - Domain classification
- BindingDB / ChEMBL - Binding affinity data
- RCSB PDB REST API - Programmatic structure queries
- PDBe-KB - Aggregated structural annotations
Output Format
- Report structures with PDB ID, resolution, method, and chain identifiers.
- Binding energies in kcal/mol with interaction fingerprints.
- Structural alignments with RMSD (in Angstroms) and TM-score.
- Residue numbering must match the canonical UniProt sequence or PDB SEQRES.
- Include PyMOL/ChimeraX commands for reproducing visualizations.
Quality Checklist
- Structure source and method (X-ray, cryo-EM, NMR, predicted) clearly stated
- Resolution or confidence metric (pLDDT) reported
- Binding site residues listed with chain and numbering
- Docking results include top poses and interaction details
- Limitations of predicted structures acknowledged where relevant
- All PDB IDs verified as valid and current
- Biological assembly vs. asymmetric unit distinguished