Strategies for compound selection.
In-house pharmaceutical collections are no longer sufficient for sampling chemical spaces. As novel bioactive chemotypes are successfully identified by virtual and high -throughput screening, the ability to rapidly sift through large numbers of chemicals prior to acquisition or experiment is required. Strategies for compound selection include some of the following steps: 1.) database assembly ('in silico' inventory); 2a.) structural integrity verification (keep unique structures only); 2b.) limited exploration of alternative chemical representations for the uniques (stereoisomers, tautomers, ionization states); 3.) property and structural filtering (remove unwanted structures); 4.) 3D-structure generation (for virtual screening or 3D-based similarity); 5a.) clustering or statistical design for selection; 5b.) similarity-based selection (if bioactives are known); 5c.) receptor-based selection (if target binding site is known); 6.) add a random subset to the final list.
Division of Biocomputing, University of New Mexico School of Medicine, BMSB61, MSC 08 4670, 1 University of New Mexico, Albuquerque, NM 87131-0001, USA.
Marius M
MM
Olah
Cristian G
CG
Bologa
Tudor I
TI
Oprea
D016000:Cluster Analysis; D003198:Computer Simulation; D016208:Databases, Factual; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D008490:Medical Informatics; D008958:Models, Molecular; D008968:Molecular Conformation; D004364:Pharmaceutical Preparations / Q000737:chemistry; D011955:Receptors, Drug / Q000737:chemistry / Q000187:drug effects; D013329:Structure-Activity Relationship
D004364:Pharmaceutical Preparations; D011955:Receptors, Drug