Protein-ligand co-design: a case for improving binding affinity between type II NADH:quinone oxidoreductase and...

Area of Science:

• Biological engineering
• Biotechnology
• Protein engineering

Background:

• Biological engineering typically designs proteins or ligands separately, limiting optimization.
• Co-designing both protein and ligand simultaneously offers enhanced functional properties.
• Ndh2 (type-II NADH dehydrogenase) interacts with quinones for extracellular electron transfer (EET).

Purpose of the Study:

• Introduce a novel co-design paradigm for simultaneous protein and ligand engineering.
• Demonstrate the co-design approach for enhancing Ndh2-quinone binding affinity.
• Highlight the benefits of a holistic perspective in protein-ligand engineering.

Main Methods:

• Developed a co-design framework for joint protein-ligand optimization.
• Applied the framework to engineer Ndh2-quinone interactions.
• Evaluated binding affinities of engineered pairings.

Main Results:

• Successfully implemented the co-design paradigm.
• Achieved enhanced binding affinities in engineered Ndh2-quinone pairs.
• Demonstrated the efficacy of holistic protein-ligand co-design.

Conclusions:

• The novel co-design paradigm effectively enhances protein-ligand binding affinity.
• Co-designing Ndh2-quinone pairings improves biosensing potential.
• A holistic approach is crucial for advanced biological engineering applications.