PDB Structure Fixing

This document provides details about HBAT’s PDB fixing capabilities, which can automatically enhance protein structures by adding missing atoms, converting residues, and cleaning up structural issues.

Overview

HBAT includes integrated PDB structure fixing capabilities that can significantly improve the quality of structural analysis by:

• Adding missing hydrogen atoms using OpenBabel or PDBFixer

• Adding missing heavy atoms using PDBFixer

• Converting non-standard residues to standard equivalents

• Removing unwanted heterogens while optionally keeping water molecules

• Improving structure quality for more accurate interaction analysis

These capabilities are particularly valuable when working with:

• Crystal structures missing hydrogen atoms

• Low-resolution structures with incomplete side chains

• NMR structures requiring standardization

• Structures containing non-standard amino acid residues

• Structures with unwanted ligands or contaminants

Why PDB Fixing is Important

Most PDB structures from X-ray crystallography lack hydrogen atoms because they are too small to be reliably determined at typical resolutions. Since hydrogen bonds are critical for:

• Protein stability: Secondary and tertiary structure maintenance

• Enzyme catalysis: Active site interactions and mechanism

• Protein-protein interactions: Interface stabilization

• Ligand binding: Drug-target interactions

Accurate hydrogen placement is essential for meaningful interaction analysis.

Supported Methods

HBAT supports two powerful methods for structure enhancement: PDBFixer and OpenBabel.

Capability	OpenBabel	PDBFixer
Add hydrogens	✓ Fast and reliable	✓ pH-dependent protonation
Add heavy atoms	✗ Not supported	✓ Complete missing atoms
Convert residues	✗ Limited	✓ Comprehensive database
Remove heterogens	✗ Not supported	✓ Selective removal
Speed	Very fast	Moderate
Dependencies	Lightweight	Requires OpenMM
Documentation	OpenBabel documentation	PDBFixer Documentation

PDB Fixing Parameters

HBAT provides comprehensive control over structure fixing through various parameters:

Core Parameters

Parameter	Default	Type	Description
fix_pdb_enabled	True	Boolean	Enable/disable PDB structure fixing
fix_pdb_method	“pdbfixer”	String	Method to use: “openbabel” or “pdbfixer”
fix_pdb_add_hydrogens	True	Boolean	Add missing hydrogen atoms
fix_pdb_add_heavy_atoms	False	Boolean	Add missing heavy atoms (PDBFixer only)
fix_pdb_replace_nonstandard	False	Boolean	Convert non-standard residues (PDBFixer only)
fix_pdb_remove_heterogens	False	Boolean	Remove unwanted heterogens (PDBFixer only)
fix_pdb_keep_water	True	Boolean	Keep water molecules when removing heterogens

Advanced Parameters

For PDBFixer, additional options are available but there are not supported by HBAT yet.

Parameter	Default	Description
pH	7.0	pH value for protonation state determination
model_residues	False	Add missing residues to complete chains
keep_ids	True	Preserve original atom numbering

References and Further Reading

OpenBabel

• O’Boyle, N.M. et al. “Open Babel: An open chemical toolbox” J. Cheminform. 3, 33 (2011)

• OpenBabel Documentation: http://openbabel.org/docs/

PDBFixer

• Eastman, P. et al. “OpenMM 4: A Reusable, Extensible, Hardware Independent Library” J. Chem. Theory Comput. 9, 461-469 (2013)

• PDBFixer Documentation: openmm/pdbfixer

Structure Preparation

• Madhavi Sastry, G. et al. “Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments” J. Comput. Aided Mol. Des. 27, 221-234 (2013)

• Shelley, J.C. et al. “A versatile approach for assigning partial charges and valence electron densities in proteins” J. Comput. Chem. 28, 1145-1152 (2007)

---

For questions about PDB fixing functionality or specific use cases, please refer to the HBAT documentation or open an issue on the GitHub repository.