The Human Immunodeficiency Virus (HIV-1), which causes Acquired Immunodeficiency Syndrome (AIDS), remains a serious health problem in the United States and around the world despite extensive research efforts into treatment and prevention.  Most vaccine candidates thus far have failed to provide immunity, which occurs through the induction of broadly neutralizing monoclonal antibodies.  The membrane proximal external region (MPER) of HIV's envelope glycoprotein (gp41) is a promising vaccine candidate, as it has high sequence conservation among strains and is transiently exposed before fusion with the host.  Several broadly neutralizing monoclonal antibodies that recognize the MPER have been discovered to date, and binding of these antibodies irreversibly inactivates the virus.  Further, the adjacent transmembrane domain (TM) and the viral membrane itself are involved in antibody binding and recognition.  Unfortunately, there are limited structural data available on the MPER for use in rational vaccine design efforts, particularly in the context of the TM and viral membrane.  Here, we present several �s-timescale, all-atom molecular dynamics simulations of the MPER+TM bound to broadly neutralizing antibodies (2F5, 4E10, 10E8, Z13e1) in a viral-like membrane in order to discern the antibody-eliciting conformations of the MPER.

Modeling the antibody-eliciting conformation of the HIV-1 gp41 MPER

248th National Meeting (2014)

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