Notably CADD methods can produce an atomic level structure-activity relationship (SAR) used to facilitate the drug design process thereby minimizing time and costs ( 3, 4). Toward the design of new antibiotics, computer-aided drug design (CADD) can be combined with wet-lab techniques to elucidate the mechanism of drug resistance, to search for new antibiotic targets and to design novel antibiotics for both known and new targets. Contributing to this is the steady rise of antibiotics drug resistance leading to the need for new antibiotics ( 1, 2). In this chapter, standard CADD protocols for both SBDD and LBDD will be presented with a special focus on methodologies and targets routinely studied in our laboratory for antibiotic drug discoveries.ĭespite the fact that numerous antibiotic drugs are available and have been routinely used for a much longer time than most other drugs, the fight between humans and the surrounding bacteria responsible for infections are ongoing and will be so for the foreseeable future. LBDD methods focus on known antibiotic ligands for a target to establish a relationship between their physiochemical properties and antibiotic activities, referred to as a structure-activity relationship (SAR), information that can be used for optimization of known drugs or guide the design of new drugs with improved activity. Such information can then be utilized to design antibiotic drugs that can compete with essential interactions involving the target and thus interrupt the biological pathways essential for survival of the microorganism(s). SBDD methods analyze macromolecular target 3-dimensional structural information, typically of proteins or RNA, to identify key sites and interactions that are important for their respective biological functions. Structure based drug design (SBDD) and ligand based drug design (LBDD) are the two general types of computer-aided drug design (CADD) approaches in existence. Computational approaches are useful tools to interpret and guide experiments to expedite the antibiotic drug design process.