New Core Features
1. **Reference-Guided Docking**
- `--reference` flag to guide docking based on known ligand poses
- `--exact-alignment` option for direct superimposition with reference structures
- `--no-local-optimization` to preserve exact alignment without refinement
2. **Flexible Residue Handling**
- `--flex-residues` option for manual selection of flexible protein side chains
- `--auto-flex` for automatic detection of flexible residues in binding sites
- `--max-flex-residues` to control number of automatically detected flexible residues
- `--max-flex-bonds` to limit rotatable bonds per residue
3. **Enhanced Search Algorithms**
- Improved rigid docking with multi-stage optimization
- Aggressive atom-by-atom refinement for better clash resolution
- Advanced clash detection and energy minimization
4. **Hardware Acceleration**
- GPU acceleration with `--use-gpu` flag
- Hybrid CPU/GPU workload balancing
- Automatic hardware tuning with `--auto-tune`
Refinement Techniques
1. **Clash Resolution Methods**
- Gentle clash relief to maintain structural integrity
- Atom-by-atom adjustment for problematic interactions
- Systematic directional shifts to escape local minima
2. **Local Optimization Improvements**
- Multi-stage optimization with decreasing step sizes
- Enhanced rotational sampling with diagonal axes
- Retreat-and-approach strategy for complex binding sites
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**Full Changelog**: https://github.com/pritampanda15/PandaDock/compare/1.0.2...1.2