Structure‐Based Approaches to Antibiotic Drug Discovery

George Nicola1, Ruben Abagyan1

1 Department of Molecular Biology, The Scripps Research Institute, La Jolla, California
Publication Name:  Current Protocols in Microbiology
Unit Number:  Unit 17.2
DOI:  10.1002/9780471729259.mc1702s12
Online Posting Date:  February, 2009
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The development of antimicrobials has advanced tremendously over the past century. However, as our production capacity increases, the threat of resistance is ever‐present. To combat this resistance, two main avenues of drug discovery are being pursued: identifying new microbial proteins for which to direct drug discovery efforts, and designing innovative drugs that target existing proteins. The advent of structural genomics research has advanced to the point of rapidly discovering novel microbial protein targets. In addition, modern tools of computational biology greatly enhance the speed and reliability of antimicrobial discovery. The various steps of this process are outlined and discussed, including virtual ligand screening, pocket identification, and compound optimization. Curr. Protoc. Microbiol. 12:17.2.1‐17.2.10. © 2009 by John Wiley & Sons, Inc.

Keywords: structure‐based drug design; computational biology; virtual ligand screening

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Table of Contents

  • Brief History of Antibacterial Discovery
  • Structural Genomics
  • What is Computational Biology?
  • Literature Cited
  • Figures
  • Tables
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Internet Resources
  Ambinter Web site. Ambinter is a provider of chemical products, including 4 million small molecules and 1500 natural products.
  Entrez Genome Project Web site. Entrez is a Web portal that allows users to search databases at the National Center for Biotechnology Information (NCBI) Website. The Genome Project seeks to provide a central repository of complete genomes to be freely available to the public.
  Interchim is continuously building their levels of inventory and currently has >700 innovative intermediates and >2.2 million compounds available for delivery. They are well known for their high throughput screening compounds.
  The J. Craig Venter Institute specializes in techniques to rapidly discover genes. They have sequenced and analyzed >50 microbial genomes.
  Molsoft is a La Jolla, California‐based company that is a primary source of new breakthrough technologies in modeling, docking, computational chemistry, and biology. They develop the ICM software that is used by many research groups in academia and the pharmaceutical industry.
  The purpose of the Chemoinformatics Tools and User Services Group at the NCI is to provide to the public structures, data, tools, programs, and other useful information. They currently have a database of >250,000 compounds.
  Rib‐X Pharmaceuticals, Inc. is a small molecule drug discovery and development company focused on the structure based design of new classes of antibiotics.
  Ryan Scientific specializes in the sale of chemicals focused on drug discovery research and used for both high‐throughput screening (HTS) and organic synthesis, using combinatorial and structure‐based techniques. Companies in their database include: ArtChem, Asinex, Bionet, ChemBlock, G&J Research, InterBioScreen, Labotest, Life Chemicals, Maybridge, Peakdale, and Specs.
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