Molecular dynamics simulation studies of Antigen-Antibody interactions
Antigen-Antibody interactions are an important area of research in biophysical chemistry and structural biology. The availability of an increasing amount of structural data of antigens and antibodies allows a better understanding of their interactions and dynamics. The binding of an antibody to the antigen involves a combination of weak non-covalent interactions. This binding may cause significant conformation changes in both antibody and antigen and these changes may involve both structural and dynamical changes. In our study, we have identified the key residues involved in hydrogen-bonding interactions and salt-bridges in Ag-Ab complex by taking an example of HIV-1 protease and F11.2.32 mAb raised against the protease. We also examined the role of CDR flexibility in binding different conformations of the same epitope sequence in peptide and protein antigens. Our results provide the basis for understanding the cross-reactivity observed between the antibody with protease and the epitope peptide from it. We also studied the role played by dynamics in the function of the protease and how control of flexibility through Ab binding and site specific mutations can inhibit its activity. The study points to a plausible method for allosteric drug control. We believe this work is of value to the existing literature on Antigen-Antibody interactions and novel drug discovery methods that involve the modulation of the dynamics of an enzyme.