Antibiotics pp 85-106 | Cite as

Computer-Aided Drug Design Methods

  • Wenbo Yu
  • Alexander D. MacKerellJr.Email author
Part of the Methods in Molecular Biology book series (MIMB, volume 1520)


Computational approaches are useful tools to interpret and guide experiments to expedite the antibiotic drug design process. 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. 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. 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). 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. 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.

Key words

Computer-aided drug design Molecular dynamics Virtual screening Docking Site identification by ligand competitive saturation SILCS Structure-activity relationship Pharmacophore Force field 



This work was supported by NIH grants CA107331 and R43GM109635, University of Maryland Center for Biomolecular Therapeutics, Samuel Waxman Cancer Research Foundation, and the Computer-Aided Drug Design (CADD) Center at the University of Maryland, Baltimore.

Conflict of interest: A.D.M. is Co-founder and CSO of SilcsBio LLC.


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© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Computer-Aided Drug Design Center, Department of Pharmaceutical Sciences, School of PharmacyUniversity of MarylandBaltimoreUSA

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