Ligands binding diffusively to protein target act as inhibitors of protein-protein interactions.

ABSTRACT: Nuclear localization signal (NLS) sequence from capsid protein of Venezuelan equine encephalitis virus (VEEV) binds to importin-α transport protein and clogs nuclear import. Prevention of viral NLS binding to importin-α may represent a viable therapeutic route. Here, we investigate the molecular mechanism by which two diffusively binding inhibitors, DP9 and DP9o, interfere with the binding of VEEV's NLS peptide to importin-α. Our study uses all-atom replica exchange molecular dynamics simulations, which probe the competitive binding of the VEEV NLS fragment, the coreNLS peptide, and the inhibitors to importin-α. Our previous simulations of non-competitive binding of the coreNLS, in which it natively binds to importin-α, are used as a reference. Both inhibitors abrogate native peptide bindi

SUBMITTER: Jeffries W 

PROVIDER: S-EPMC12456801 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature