Investigation of radezolid interaction with non-canonical chloramphenicol binding site by molecular dynamics simulations

Radezolid is a promising antibiotic of oxazolidinone family, which is able to overcome effect of some linezolid resistance mechanisms of bacterial ribosomes. The structure of the radezolid complex with ribosomes was never published but, by analogy with linezolid, it is considered to prevent the binding of aminoacyl–tRNA to the A–site of the ribosome large subunit. However, as with linezolid, it can be assumed that radezolid binds to the alternative binding site existing in the A,A/P,P–ribosome. In the present article we have investigated this issue by molecular dynamics simulations and proposed the structure of the radezolid complex with a E. coli ribosome, which is consistent with available data of biochemical investigations of radezolid action. [Display omitted] •Structures of radezolid-ribosome complexes were never published.•Radezolid is able to bind non-canonic chloramphenicol binding site.•This binding pose was revealed with docking and MD simulations.•This pose was obtained for ribosome binding aminoacyl- and peptidyl-tRNA.•This pose is in line with data about oxazolidinone resistance mutations and Cfr methyltransferase associated oxazolidinone resistance.