Effective in silico prediction of new oxazolidinone antibiotics: force field simulations of the antibiotic-ribosome complex supervised by experiment and electronic structure methods.

ABSTRACT: We propose several new and promising antibacterial agents for the treatment of serious Gram-positive infections. Our predictions rely on force field simulations, supervised by first principle calculations and available experimental data. Different force fields were tested in order to reproduce linezolid's conformational space in terms of a) the isolated and b) the ribosomal bound state. In a first step, an all-atom model of the bacterial ribosome consisting of nearly 1600 atoms was constructed and evaluated. The conformational space of 30 different ribosomal/oxazolidinone complexes was scanned by stochastic methods, followed by an evaluation of their enthalpic penalties or rewards and the mechanical strengths of the relevant hydrogen bonds (relaxed force constants; compliance constants). T

SUBMITTER: Grunenberg J 

PROVIDER: S-EPMC4902031 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature