Roles of variable linker length in dual acting virucidal entry inhibitors on HIV-1 potency via on-the-fly free energy molecular simulations.

ABSTRACT: The Dual-Acting Virolytic Entry Inhibitors, or DAVEI's, are a class of recombinant chimera fusion proteins consisting of a lectin, a flexible polypeptide linker, and a fragment of the membrane-proximal external region (MPER) of HIV-1 gp41. DAVEIs trigger virolysis of HIV-1 virions through interactions with the trimeric envelope glycoprotein complex (Env), though the details of these interactions are not fully determined as yet. The purpose of this work was to use structural modeling to rationalize a dependence of DAVEI potency on the molecular length of the linker connecting the two components. We used temperature accelerated molecular dynamics and on-the-fly parameterization to compute free energy versus end-to-end distance for two different linker lengths, DAVEI L0 (His₆ ) and

SUBMITTER: Gossert ST 

PROVIDER: S-EPMC7586904 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature