Molecular Dynamics Simulation of the Antigen–Antibody Complex Formation Process between Hen Egg-White Lysozyme and HyHEL-10

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Abstract We performed molecular dynamics (MD) simulations (57 µs in total) to examine the formation of a typical antigen–antibody complex, that of hen egg-white lysozyme (HEL) and its antibody, HyHEL-10. We observed that HEL and HyHEL-10 successfully formed native complexes in several MD simulations. Energetic analyses showed that native complexes tend to have lower interaction energies than most of the other encounter complexes, which is a useful feature for computational complex structure prediction. In the stabilization process, we found that the N32L residue underwent a characteristic conformational change (structural locking), which significantly enhanced the interaction energy. In addition, we performed MD simulations for the N32LD mutein. The results showed that the N32LD mutation enhanced the electrostatic interaction and accelerated the encounter dynamics. However, in the stabilization process, the N32LD mutation deteriorated the structural locking role of N32L, and therefore we could not find any specific conformational change to stabilize the complex structure. The resultant loose feature of the N32LD complex is consistent with experimental observations that the N32LD mutation decreases binding affinity but leads to a large entropic gain.