Antigen-antibody recognition. Model calculations

Area of Science:

• Biochemistry and Molecular Biology
• Immunology
• Computational Biophysics

Background:

• Antigen-antibody interactions are crucial for immune responses.
• Understanding the molecular basis of binding affinity is key to developing therapeutics.
• Specific amino acid residues in antibodies and antigens significantly influence binding.

Purpose of the Study:

• To calculate the free energy of antigen-antibody binding for specific antibody-antigen complexes.
• To identify key residues contributing to binding affinity in both antibodies and antigens.
• To investigate the role of tyrosine and tryptophan residues in antibody binding.

Main Methods:

• Free energy calculations were performed for HyHEL-5, HyHEL-10, and D1.3 antibody-antigen complexes.
• Binding free energies were analyzed per residue for antibody light (L) and heavy (H) chains.
• Binding free energies were also analyzed per residue for the antigen (lysozyme).

Main Results:

• Tyrosine (TYR) and tryptophan (TRP) residues in antibody complementarity-determining regions (CDRs) were found to enhance antigen binding.
• The composition of residues contributing the major part of the binding free energy differs between antibodies and antigens.
• Specific residue contributions to binding energy were quantified for the studied complexes.

Conclusions:

• TYR and TRP residues play a significant role in the antigen-binding capacity of antibody CDRs.
• Antibody and antigen interfaces have distinct residue compositions that drive binding free energy.
• These findings provide insights into the molecular mechanisms of antibody-antigen recognition.