Atomic-scale characterization of mature HIV-1 capsid stabilization by inositol hexakisphosphate (IP₆).

ABSTRACT: Inositol hexakisphosphates (IP₆) are cellular cofactors that promote the assembly of mature capsids of HIV. These negatively charged molecules coordinate an electropositive ring of arginines at the center of pores distributed throughout the capsid surface. Kinetic studies indicate that the binding of IP₆ increases the stable lifetimes of the capsid by several orders of magnitude from minutes to hours. Using all-atom molecular dynamics simulations, we uncover the mechanisms that underlie the unusually high stability of mature capsids in complex with IP₆ We find that capsid hexamers and pentamers have differential binding modes for IP₆ Ligand density calculations show three sites of interaction with IP₆ including at a known capsid inhibi

SUBMITTER: Yu A 

PROVIDER: S-EPMC7494349 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature