Supercomputer simulation reveals possible solutions to antibiotic resistance

Antibiotic resistance is here, and researchers have been scrambling to find a possible solution to fight back. In simulations conducted on a supercomputer at the Department of Energy's Oak Ridge National Laboratory (ORNL) in Tennessee, researchers have uncovered a new class of drug candidates that might be the leading weapon in fighting antibiotic resistance.

Researchers from the University of Oklahoma with ORNL, University of Tennessee and Saint Louis University have combined a number of lab experiments with supercomputer modeling to seek the molecules capable of boosting antibiotics effects on dangerous bacteria.

"The supercomputing power of Titan allowed us to perform large-scale simulations of the drug targets and to screen many potential compounds quickly," said Helen Zgurskaya, head of the University of Oklahoma's Antibiotic Discovery and Resistance Group, who led the study. "The information we received was combined with our experiments to select molecules that were found to work well, and this should drastically reduce the time needed to move from the experimental phase to clinical trials."

The simulations revealed four new chemicals capable of interfering with the efflux pumps within a bacterium. The efflux pumps, being the direct cause of antibiotic resistance within the AcrA protein, are able to connect two proteins in a tunnel through the bacterial cell envelope. The AcrA protein was signaled out by researchers because if they are able to disrupt the connection of proteins, they would stop the efflux pump.

"As a first in this field, we proposed the approach of essentially 'screwing up' the efflux pump's protein assembly, and this led to the discovery of molecules with a new type of antibacterial activity," said co-author Jeremy Smith, director of the UT-ORNL Center for Molecular Biophysics. "In contrast to previous approaches, our new mechanism uses mechanics to revive existing antibiotics' ability to fight infection."