Virtual ligand screening: strategies, perspectives and limitations.
In contrast to high-throughput screening, in virtual ligand screening (VS), compounds are selected using computer programs to predict their binding to a target receptor. A key prerequisite is knowledge about the spatial and energetic criteria responsible for protein-ligand binding. The concepts and prerequisites to perform VS are summarized here, and explanations are sought for the enduring limitations of the technology. Target selection, analysis and preparation are discussed, as well as considerations about the compilation of candidate ligand libraries. The tools and strategies of a VS campaign, and the accuracy of scoring and ranking of the results, are also considered.
Klebe
Gerhard
G
Institute of Pharmaceutical Chemistry, University of Marburg, Marbacher Weg 6, D-35032 Marburg, Germany. klebe@mailer.uni-marburg.de
D001665:Binding Sites; D003198:Computer Simulation; D003460:Crystallization; D019992:Databases as Topic; D015195:Drug Design; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D011522:Protons; D012984:Software; D014867:Water / Q000737:chemistry
D008024:Ligands; D011506:Proteins; D011522:Protons; D014867:Water