High correlation between HADDOCKing score and SMD rupture force in iBRAB Fab model and IAV HA protein systems

Bioinformatics for Rational drug design

Therapeutic monoclonal antibodies represent a potent strategy for combating acute infectious diseases. However, identifying the most efficacious antibodies among the vast human variants necessitates extensive time and advanced technological resources. The iBRAB method, previously introduced, aims to harness studied antibodies to engineer a broad-spectrum antibody capable of neutralizing antigens from diverse strains of Influenza A virus. Initially, we assessed the predictive performance of HADDOCK in delineating binding configurations across a range of protein complexes. This investigation again delves into the intricate interplay between computational docking forecasts and the mechanical resilience of protein-protein interactions by utilizing the iBRAB method in conjunction with Steered Molecular Dynamics (SMD) simulations. Emphasis was placed on optimizing pulling parameters, such as force and rate, within SMD simulations to ensure the fidelity of rupture force measurements. Our findings reveal a robust positive correlation between the docking scores forecasted by HADDOCK and the rupture forces observed in SMD simulations. This correlation suggests that complexes identified by HADDOCK as possessing heightened binding affinity also exhibit enhanced mechanical stability, as evidenced by the substantial force needed for separation. This integrated approach, amalgamating the iBRAB method for protein preparation, HADDOCK docking predictions, and SMD simulations with optimized pulling parameters, emerges as a valuable tool for elucidating the intricate relationship between binding affinity and mechanical resilience in protein-protein interactions

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