ZEAL

ZEAL performs protein structure alignment by evaluating global and local surface shape similarity using 3D Zernike-Canterakis functions to enable comparison of protein function, binding sites, and evolutionary relationships.

Key Features:

• Shape-Based Superposition: ZEAL utilizes 3D Zernike-Canterakis functions to represent molecular surfaces and performs global and local alignments based on shape resemblance rather than Cartesian atomic coordinates.
• Surface Shape Emphasis: By focusing on surface geometry, ZEAL aligns proteins with similar surface shapes even when their overall fold structures differ substantially.
• Performance and Benchmarking: In benchmarks on proteins with identical folds, ZEAL outperformed other shape-based superposition methods and produced alignments comparable in quality to coordinate-based tools such as TM-align.
• Handling Divergent Proteins: ZEAL aligns proteins that exhibit limited sequence and backbone-fold similarity, facilitating identification of convergent evolution and detailed comparison of surface features and binding sites.
• Functional Insights: ZEAL correlates global surface shape similarity with protein function and identifies functional categories with elevated shape similarity, notably DNA-binding proteins.

Scientific Applications:

• Comparative Structural Analysis: Enables detailed comparison of highly divergent proteins to infer evolutionary relationships and functional convergence.
• Binding Site Investigation: Superimposes proteins by surface shape to facilitate precise examination of binding sites for molecular interaction analysis and drug design.
• Functional Prediction: Associates shape similarity with specific protein functions to support prediction of roles for uncharacterized proteins.

Methodology:

ZEAL represents protein molecular surfaces using 3D Zernike-Canterakis functions and aligns structures by comparing their Zernike-based shape descriptors.