patcHwork

patcHwork identifies amino acids and residue clusters whose protonation and charge states change between two specified pH values to analyze pH-dependent effects on noncovalent interactions and protein structure.

Key Features:

• Charge Shift Identification: Identifies amino acids that undergo charge shifts between two specified pH values to map residue-specific protonation changes.
• Sequence Analysis (FASTA): Applies the Henderson-Hasselbalch equation to predict pH-sensitive residues from FASTA input supporting up to 10,000 amino acid sequences (maximum size 20MB).
• Structural Analysis (PDB): Analyzes single PDB files or multiple PDBs in a zip archive (up to 20MB) using PDB2PQR and PROPKA to compute structure-based pKa and protonation states.
• Noncovalent Bond Analysis: Determines affected noncovalent interactions, including salt bridges, hydrogen bonds, and aromatic interactions (pi-pi and cation-pi), upon pH change.
• Patch Concept: Detects "patches," defined as clusters of pH-sensitive residues in close proximity on the protein surface.

Scientific Applications:

• pH-dependent protein function analysis: Maps residue- and patch-level protonation changes to infer mechanistic effects of pH on protein structure and interaction networks.
• Enzymology: Identifies pH-sensitive residues and patches that may modulate catalytic activity through altered charge and noncovalent interactions.
• Drug design: Highlights pH-dependent changes in interaction networks and surface patches relevant to ligand binding and target modulation.
• Molecular biology: Provides residue-level insights into how pH shifts can influence protein stability, interactions, and functional states.

Methodology:

Calculates residue protonation at the sequence level using the Henderson-Hasselbalch equation, computes structure-based pKa and protonation with PDB2PQR and PROPKA, compares protonation/charge states between two user-defined pH values, identifies disrupted noncovalent interactions (salt bridges, hydrogen bonds, pi-pi and cation-pi), and clusters pH-sensitive residues into proximity-based patches.