Structure-Based Strategies for Drug Design and Discovery

• Published in: Science (American Association for the Advancement of Science) Vol. 257; no. 5073; pp. 1078 - 1082
• Main Author: Kuntz, Irwin D.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 21.08.1992; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Acquired Immunodeficiency Syndrome - drug therapy; Antiviral Agents - chemical synthesis; Biological and medical sciences; Chemicals; Computers; Database design; Docks; Drug Design; Drug Resistance, Microbial; Drugs; Enzymes; General pharmacology; Lead; Ligands; Medical sciences; Molecular Structure; Molecules; Narcotics; Organic Chemistry; Pharmaceutical industry; Pharmaceutical research; Pharmacology. Drug treatments; Physicochemical properties. Structure-activity relationships; Product development; Protein structure; Proteins; R&D; Receptors; Research & development; Software; Structure; Drug; Molecular structure; AIDS; Review; Infection; Design; Proteins; Resistance; Structure activity relation; Viral disease; Antiviral; Bacteria; Antibacterial agent; Nucleic acid; Computer aid; Biological receptor
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.257.5073.1078

Most drugs have been discovered in random screens or by exploiting information about macromolecular receptors. One source of this information is in the structures of critical proteins and nucleic acids. The structure-based approach to design couples this information with specialized computer programs to propose novel enzyme inhibitors and other therapeutic agents. Iterated design cycles have produced compounds now in clinical trials. The combination of molecular structure determination and computation is emerging as an important tool for drug development. These ideas will be applied to acquired immunodeficiency syndrome (AIDS) and bacterial drug resistance.