Methods virtual screening

Both ligand- and structure-based methods can be applied in virtual screening. An example of a workflow chart for virtual screening is depicted in Figure 10,4-3. 

H.-J. Bohm, G. Schneider (Eds.), Virtual screening for bioactive molecules, in Methods and Principles in Medicinal Chemistry, Vol. 10, R. Marmhold, H. Kubinyi, H. Timmerman (Eds.), Wiley-VCH, Weinheim, 2000, pp. 1-307... 

Wilton DJ, Willett P, Mullier G, Lawson K. Comparison of ranking methods for virtual screening in lead-discovery programmes. J Chem Inf Comput Sci 2003 43 469-74. 

As the availability of crystal structures increased in the early 1990s, a number of experimental and computational methods were developed to use the structure of the protein target as a route to discover novel hit compounds. The methods include de novo design, virtual screening, and fragment-based discovery. These developments are covered in more detail in the later chapters of this book, but their main features can be summarized as follows. 

Virtual screening uses computational docking methods to assess which of a large database of compounds will fit into the unliganded structure of the target protein. Current protocols and methods can, with up to 80% success, predict the binding position and orientation of ligands that are known to bind... 

Kitchen DB, Decornez H, Furr JR, Bajorath J. Docking and scoring in virtual screening for drug discovery methods and applications. Nat Rev Drug Discov 2004 3(ll) 935-49. 

Bohm HI, Schneider G, editors. Virtual screening for bioactive molecules (Vol. 10 of Mannhold R, Kubinyi H, Timmerman H, editors. Methods and principles in medicinal chemistry). Weinheim Wiley-VCH, 2000. 

Schneider G, Bohm H J. Virtual screening and fast automated docking methods. Drug Discov Today 2002 7 64-70. 

Another group has evaluated self-organizing maps [63] and shape/ pharmacophore models [64]. They developed a new method termed SQUIRREL to compare molecules in terms of both shape and pharmacophore points. Thus from a commercial library of 199,272 compounds, 1926 were selected based on self-organizing maps trained on peroxisome proliferator-activated receptor a (PPARa) "activity islands." The compounds were further evaluated with SQUIRREL and 7 out of 21 molecules selected were found to be active in PPARa. Furthermore, a new virtual screening technique (PhAST) was developed based on representation of molecules as text strings that describe their pharmacophores [65]. 

Roche, O., Trube, G., Zuegge, J., Pfrimlin, P., Alanine, A. and Schneider, G. (2002) A virtual screening method for prediction of the HERG potassium... 

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