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ProCogGraph: a graph-based mapping of cognate ligand domain interactions
Matthew Crown1, Matthew Bashton1
1Hub for Biotechnology in the Built Environment, Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, United Kingdom.
Bioinformatics Advances
|November 15, 2024
Summary
ProCogGraph is a new graph database mapping protein domain-cognate ligand interactions in the Protein Data Bank (PDB). It enhances understanding of evolution, protein design, and systematically annotates enzyme functions.
Area of Science:
- Biochemistry
- Structural Biology
- Bioinformatics
Background:
- Understanding protein domain-cognate ligand interactions is crucial for evolutionary studies and protein design.
- Existing databases for these interactions have not kept pace with the significant growth of the Protein Data Bank (PDB).
- New computational tools for analyzing structural similarity and contacts have become available.
Purpose of the Study:
- To present ProCogGraph, a novel graph database of domain-cognate ligand mappings derived from PDB structures.
- To build upon previous work (PROCOGNATE) using data-driven methods to define interaction thresholds and modes.
- To explore novel aspects of these interactions, including ligand chemical similarity and the impact of domain combinations on binding.
Main Methods:
- Developed a graph database (ProCogGraph) to store and analyze domain-cognate ligand interactions from PDB data.
- Employed data-driven approaches to establish thresholds for interaction modes.
- Investigated chemical properties of bound ligands and the influence of domain pairings on binding specificity.
Main Results:
- ProCogGraph systematically maps domain-cognate ligand interactions within the PDB.
- The database reveals insights into the chemical similarity of cognate ligands and the role of domain combinations in binding.
- ProCogGraph successfully enhances specificity for partial Enzyme Commission (EC) IDs by leveraging cognate ligand information.
Conclusions:
- ProCogGraph provides a valuable resource for studying protein-ligand interactions and their evolutionary implications.
- The database facilitates advancements in protein design and functional annotation.
- ProCogGraph offers a systematic method for annotating enzyme functions using cognate ligand data.
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