Ab-Ligity: identifying sequence-dissimilar antibodies that bind to the same epitope

Area of Science:

• Immunology
• Structural Biology
• Bioinformatics

Background:

• Determining antibody-antigen complex structures provides detailed interaction insights but is costly and difficult.
• Epitope mapping and binning offer alternative experimental data but lack resolution for precise interaction comparison.
• Existing computational methods often rely on sequence similarity, failing to identify functionally similar but sequence-distant antibodies.

Purpose of the Study:

• To develop a structure-based similarity measure, Ab-Ligity, for assessing antibody-antigen interfaces.
• To evaluate Ab-Ligity's capability in identifying antibodies that target highly similar epitopes, especially those with sequence dissimilarity.
• To compare Ab-Ligity's performance against existing protein interface comparison tools.

Main Methods:

• Ab-Ligity utilizes predicted antibody paratopes on model antibody structures.
• The method assesses the similarity of antibody-antigen interfaces.
• Performance was evaluated on identifying antibodies binding to similar epitopes, including sequence-distant antibodies.

Main Results:

• Ab-Ligity achieved high precision (0.95) and recall (0.69) in identifying sequence-dissimilar antibodies targeting similar epitopes.
• The tool demonstrated superior performance compared to InterComp, a general protein interface comparison tool, for antibody cases.
• Ab-Ligity processed antibody interface comparisons significantly faster than InterComp.

Conclusions:

• Ab-Ligity effectively identifies diverse antibodies binding to similar epitopes, overcoming limitations of sequence-based methods.
• The tool enables the discovery of functionally related but sequence-dissimilar antibodies from large datasets like immune repertoires.
• Ab-Ligity offers a faster and more accurate approach for analyzing antibody-antigen interactions.