Similarity Based Virtual Screening:  A Tool for Targeted Library Design

• Published in: Journal of medicinal chemistry Vol. 49; no. 7; pp. 2353 - 2356
• Main Authors: Alvesalo, Joni K. O, Siiskonen, Antti, Vainio, Mikko J, Tammela, Päivi S. M, Vuorela, Pia M
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 06.04.2006
• Subjects: Acetamides - chemical synthesis; Acetamides - chemistry; Acetamides - pharmacology; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacillus subtilis - enzymology; Benzamides - chemical synthesis; Benzamides - chemistry; Benzamides - pharmacology; Benzimidazoles - chemical synthesis; Benzimidazoles - chemistry; Benzimidazoles - pharmacology; Binding Sites; Biological and medical sciences; Cell Line; Cell Survival - drug effects; Chlamydophila pneumoniae; Chlamydophila pneumoniae - drug effects; Chlamydophila pneumoniae - enzymology; Crystallography, X-Ray; Databases, Factual; Drug Design; Humans; Ligands; Medical sciences; Methyltransferases - antagonists & inhibitors; Methyltransferases - chemistry; Models, Molecular; Oxadiazoles - chemical synthesis; Oxadiazoles - chemistry; Oxadiazoles - pharmacology; Pharmacology. Drug treatments; Protein Conformation; Pyridines - chemical synthesis; Pyridines - chemistry; Pyridines - pharmacology; Chlamydia pneumoniae; Targeting; Similarity; Lung; Active site; Cytotoxicity; Respiratory system; Modeling; Thiophene derivatives; Structure activity relation; Three dimensional structure; Chemical compound library; Molecular model; Chlamydiales; Bacteria; Human; Chlamydiaceae; Enzyme; Transferases; Virtual screening; In vitro; Cell line; Benzimidazole derivatives; Benzamide derivatives; Carboxamide
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm051209w

High throughput screening drug discovery utilizes large and expensive compound libraries. As an alternative, a smaller targeted library can be constructed with the aid of the 3D structure of the target molecule. We used the X-ray crystal structure of a protein homologous to the selected target in creation of a small focused library and evaluated inhibition potential of this library against Chlamydia pneumoniae, a common pathogen recently linked to atherosclerosis and risk of myocardial infarction.