IgG1-b12–HIV-gp120 Interface in Solution: A Computational Study

The use of broadly
neutralizing antibodies against human immunodeficiency
virus type 1 (HIV-1) has been shown to be a promising therapeutic
modality in the prevention of HIV infection. Understanding the b12–gp120
binding mechanism under physiological conditions may assist the development
of more broadly effective antibodies. In this work, the main conformations
and interactions between the receptor-binding domain (RBD) of spike
glycoprotein gp120 of HIV-1 and the IgG1-b12 mAb are studied. Accelerated
molecular dynamics (aMD) and ab initio hybrid molecular dynamics have
been combined to determine the most persistent interactions between
the most populated conformations of the antibody–antigen complex
under physiological conditions. The results show the most persistent
receptor-binding mapping in the conformations of the antibody–antigen
interface in solution. The binding-free-energy decomposition reveals
a small enhancement in the contribution played by the CDR-H3 region
to the b12–gp120 interface compared to the crystal structure.