Leveraging structural information for the discovery of new drugs: computational methods.
Escalating problems with drug resistance continue to compromise the effectiveness of commercial antibiotics, necessitating the search for novel classes of antimicrobial agents. To circumvent problems with resistance, a multitarget single-pharmacophore approach has been employed to discover inhibitors that possess balanced activity against multiple target enzymes. In this chapter, we examine the application of computational techniques, in particular, structure-based drug design approaches, to design new dual-targeting antibacterial agents against bacterial topoisomerases.
Lawrence Livermore National Laboratory, Physical and Life Sciences Directorate, Livermore, CA, USA.
Toan B
TB
Nguyen
Sergio E
SE
Wong
Felice C
FC
Lightstone
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000201:enzymology; D019295:Computational Biology / Q000379:methods*; D018360:Crystallography, X-Ray; D027081:DNA Gyrase / Q000737:chemistry; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D059005:Topoisomerase II Inhibitors; D027081:DNA Gyrase