The investigation of antibody affinity maturation and its effects on antigen binding is important with respect to understanding the regulation of the immune response. To shed light on this crucial process, we analyzed two Igs neutralizing the human cytomegalovirus: the primary germline antibody M2J1 and its related mature antibody 8F9. Both antibodies target the AD-2S1 epitope of the gB envelope protein and are considered to establish similar interactions with the cognate antigen. We used molecular dynamics simulations to understand the effect of mutations on the antibody–antigen interactions. The results provide a qualitative explanation for the increased 8F9 peptide affinity compared with that of M2J1. The emerging atomistic-detailed description of these complexes reveals the molecular effects of the somatic hypermutations occurring during affinity maturation.
Bibliographical noteKAUST Repository Item: Exported on 2020-10-01
Acknowledged KAUST grant number(s): k1038
Acknowledgements: The simulations were performed using the computational resources provided by the KAUST Supercomputer Laboratory (project k1038). We thank the support of NVIDIA Corporation for the award of the NVIDIA Hardware Grant (Tesla K40 GPU) used for this research. This article is dedicated to Professor Anna Tramontano, for her very enlightening and inspiring view on research, in memoriam.
This publication acknowledges KAUST support, but has no KAUST affiliated authors.