Virtual screening
From DrugPedia: A Wikipedia for Drug discovery
Virtual Screening is the process of screen large no. of molecule using in-silico methods. It involves the use of high-performance computing to analyze large databases of chemical compounds in order to identify possible drug candidates, and is a technology that complements current advances in high-throughput chemical synthesis and biological assay. It brings a more focused approach to HTS by using computational analysis to select a subset of compounds considered to be appropriate for a given protein target. Clearly, this strategy implies that some information is available regarding either the nature of the ligand binding site or the type of ligand that is expected to bind productively, or both. Virtual screening encompasses a variety of computational screens, from the simplistic to the sophisticated, and, hence, can usefully exploit different types of information describing the receptor.
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Methods
There are two methods for virtual screening.
- Structure Based Screening
- Ligand Based Screening
Structure Based Screening
Structure based screening is based on the method of docking of ligands molecule from chemical database with a known receptor/target molecule.
Ligand Based Screening
In this case first we build the 3-D structure of receptor molecule and calculate their pharmacophore properties like molecular weight, hydrophobicity etc. These properties is then used to search the database of chemical compound to filter such compounds that have comparable properties.
A pharmacophore is a simplified 3-D description of the key structural features of a set of known ligands or of the target receptor. The structural features are usually described in terms of discrete hydrogen bond donors or acceptors, lipophilic centers, ring centroids, and so on, separated in terms of distances (more usually, distance ranges). Typically these sites are derived from a set of ligands and, hence, represent those features, common to the ligands, that are deemed to be relevant to activity. A pharmacophore is readily used to search a database of chemical structures. These structures need to contain 3-D models, and preferably a conformationally flexible search is necessary so that compounds are not rejected on the trivial basis that an inappropriate conformer is stored in the database.
References
1) Waszkowycz B, Perkins TDJ, Sykes RA, Li J (2001). "Large-scale virtual screening for discovering leads in the postgenomic era". IBM Systems Journal 40 (2): 360-376.
