Virtual ligand screening: strategies, perspectives and limitations

By Gerhard Klebe. 2006

639 citations recorded by the source corpus.

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.

Subfields: Computational Theory and Mathematics, Molecular Biology, Computational Chemistry & Drug Discovery

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Citations in the corpus

Molecular Docking and Structure-Based Drug Design Strategies (2015, background): “In approximately 65% of the crystallographic protein-ligand complexes, at least one water molecule is involved in ligand-receptor recognition [108].”
Computer-aided drug discovery and development (CADDD): in silico-chemico-biological approach. (2008, background): “However, CADDD is still an evolving technology and has number of limitations [9,28,65].”
In silico pharmacology for drug discovery: methods for virtual ligand screening and profiling (2007, methodology): “Target-based virtual screening methods depend on the availability of structural information of the target, that being either determined experimentally or derived computationally by means of homology modelling techniques (Shoichet, 2004; Klebe, 2006).”
New design strategies for antidepressant drugs (2013, background): “Ensemble docking, which employs multiple conformations of the target protein, is suggested to improve enrichment in the structure-based VS studies [102].”
Molecular docking and ligand specificity in fragment-based inhibitor discovery (2009, background): “This reflects two concerns in the community: first, fragments may be more promiscuous in their binding modes than larger 'drug-like' molecules, and this is difficult to predict; second, docking scoring functions are inaccurate even for the larger molecules against which they have often been paramete”
The enumeration of chemical space (2012, methodology): “29 , 30 Because virtual screening relies on the implementation of theoretical models, the method is very similar to rational design, but is better described as rational choosing.”