Binding hot-spots in an antibody-ssDNA interface: a molecular dynamics study.

Area of Science:

• Immunology and Structural Biology
• Computational Biophysics

Background:

• Antigen-antibody interactions are crucial for understanding immune responses.
• Elucidating antibody-ssDNA complex mechanics is vital in immunology.

Purpose of the Study:

• Investigate the dissociation mechanisms of the human systemic lupus erythematosus antibody-ssDNA complex.
• Identify key residues and interactions governing complex stability.

Main Methods:

• Molecular dynamics simulations with an explicit water model.
• Potential of Mean Force (PMF) calculations for dissociation energy.
• Molecular Mechanics with the Poisson-Boltzmann and Solvent Accessible Surface Area (MM-PBSA) method.

Main Results:

• Identified 8 critical residues (Gly44, Asn54, Arg98, Tyr100, Asp101, Tyr32, Tyr49, Asn50) and 5 inter-protein hydrogen bonds impacting interaction.
• Dissociation binding affinity calculated as 7.96 ± 0.33 kcal mol⁻¹, closely matching experimental values (7.00 kcal mol⁻¹).
• MM-PBSA binding affinity determined to be 9.12 ± 1.65 kcal mol⁻¹.

Conclusions:

• The identified residues and hydrogen bonds significantly influence antibody-ssDNA complex stability.
• Findings provide a basis for protein engineering of antibody-ssDNA structures.
• Potential for developing novel bioactive antibody analogues with enhanced properties.