Conformational and dynamical basis for cross-reactivity observed between anti HIV-1 protease antibody with protease and an epitope peptide from it

F11.2.32 is a monoclonal antibody raised against HIV-1 protease and it inhibits protease activity. While the structure of the epitope peptide in complex with the antibody is known, how protease interacts with the antibody is not known. In this study, we model the conformational features of the free and bound epitope peptide and protease-antibody interactions. We find through our simulations, that the free epitope peptide P36-46 samples conformations akin to the bound conformation of the peptide in complex with the Ab, with a β-turn conformation sampled by the 38LPGR41 sequence highlighting the role of inherent conformational preferences of the peptide. Further, to determine the interactions present between the protease and antibody, we docked the protease in its conformation observed in the crystal structure, onto the antibody and simulated the dynamics of the complex in explicit water. We have identified the key residues involved in hydrogen-bond interactions and salt-bridges in Ag-Ab complex and examined the role of CDR flexibility in binding different conformations of the same epitope sequence in peptide and protein antigens. Thus, our results provide the basis for understanding the cross-reactivity observed between the antibody with protease and the epitope peptide from it.