A tale of two loops: polarizable molecular dynamics simulations of two HIV-1 G-quadruplexes in the long terminal repeat

Abstract

Human immunodeficiency virus (HIV) impacts over one million people in the United States alone, but even with such high prevalence there is still no cure for this disease. HIV-1, the etiological agent of HIV, is a retrovirus with a single-stranded RNA genome that relies on the 5’-long terminal repeat (5’-LTR) to act as a promoter for viral replication. In the 5’-LTR, the guanine-rich U3 region can fold into G-quadruplex (GQ) structures. GQs are noncanonical nucleic acid structures stabilized by Hoogsteen hydrogen-bonded guanine tetrads that stack upon each other to form an electronegative core that is further stabilized by cations.