Antibodies are composed of light and heavy chains, both of which have constant and variable regions. The diversity, specific binding ability and therapeutic potential of antibodies are determined by hypervariable loops called complementarity-determining regions (CDRs), with the other regions being the framework regions.
Objective
To investigate the key amino acid patterns in various antibody regions in the human therapeutic antigen-antibody (Ag-Ab) complexes collected from the Thera-SAbDab database.
Method
The study focuses on identifying the amino acid frequency, diversity index in CDRs, paratope-epitope amino acid interactions, amino acid bond formation frequency, and bond types among selected therapeutic Ag-Ab complexes.
Results
The results revealed that Ser is highly distributed in the overall light chain CDRs while Gly is highly distributed in the heavy chain CDRs. CDR profiling analysis indicated that the average amino acid diversity in heavy chain CDRs is 60% to 70%, while in the light chain, it is 50% to 60%. Aromatic residues such as Tyr, Trp and Phe are the top contributors to these paratope-epitope interactions in the light and heavy chains. Moreover, we examined the frequency of amino acids in light and heavy chains of Ag-Ab complexes. Importantly, the outcome of this study leverages the in depth analysis on single residues, dipeptides, and tripeptides for the therapeutic Ag-Ab complexes.
Conclusion
We conclude that the amino acid frequency and interaction analysis centered on therapeutic Ag-Ab complexes will benefit antibody engineering parameters such as antibody design, optimization, affinity maturation, and overall antibody development.
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