Amino Acids Frequency and Interaction Trends: Comprehensive Analysis of Experimentally Validated Viral Antigen-Antibody Complexes.

Abstract

Antibodies have specific binding capabilities and therapeutic potential for treating various diseases, including viral infections. The amino acid composition of the hypervariable complementarity determining regions (CDR) loops and the framework regions (FR) are the determining factors for the affinity and therapeutic efficacy of the antibodies. In this study selected and curated, 77 viral antigen-human antibody complexes from Protein data bank from the Thera-SAbdab database were analyzed. The results revealed diversity indices within specific CDR regions, amino acid frequencies, paratope-epitope interactions, bond formations, and bond types among the analyzed viral Ag-Ab complexes. The finding revealed that Ser, Gly, Tyr, Thr, and Phe are prominently present in the antibody CDRs. Analysis of CDR profiles indicated an average amino acid diversity of 60-80% in heavy chain CDRs and 45-60% in light chain CDRs. Aromatic residues, particularly Tyr, Phe, and Trp showed significant involvement in the paratope-epitope interactions in the heavy chain, while Tyr, Ser, and Thr were key contributors in the light chain. Furthermore, the study examined the occurrence of amino acids in both light and heavy chains of viral Ag- human Ab complexes, analyzing the presence of amino acids as single residues, dipeptides and tripeptides. The analysis is crucial for enhancing the antibody engineering processes including, design, optimization, affinity enhancement, and overall antibody development.