Editing Drug design (section)

==== Binding site identification ====

[[Binding site]] identification is the first step in structure based design.<ref name = "Yuan_2013"/><ref name = "Leis_2010">{{cite journal | vauthors = Leis S, Schneider S, Zacharias M | title = In silico prediction of binding sites on proteins | journal = Current Medicinal Chemistry | volume = 17 | issue = 15 | pages = 1550–1562 | year = 2010 | pmid = 20166931 | doi = 10.2174/092986710790979944 }}</ref>  If the structure of the target or a sufficiently similar [[protein homology|homolog]] is determined in the presence of a bound ligand, then the ligand should be observable in the structure in which case location of the binding site is trivial.  However, there may be unoccupied [[allosteric modulator|allosteric binding sites]] that may be of interest.  Furthermore, it may be that only [[wikt:apoprotein|apoprotein]] (protein without ligand) structures are available and the reliable identification of unoccupied sites that have the potential to bind ligands with high affinity is non-trivial. In brief, binding site identification usually relies on identification of [[wikt:concave|concave]] surfaces on the protein that can accommodate drug sized molecules that also possess appropriate "hot spots" ([[hydrophobic]] surfaces, [[hydrogen bonding]] sites, etc.) that drive ligand binding.<ref name = "Yuan_2013"/><ref name = "Leis_2010"/>