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

J Mol Graph Model. 2021 Mar 21;105:107902. doi: 10.1016/j.jmgm.2021.107902. Online ahead of print.

ABSTRACT

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.

PMID:33798835 | DOI:10.1016/j.jmgm.2021.107902