Chemistry Reference
In-Depth Information
design there is a reduction of time-consuming expensive experimental synthesis
and characterization [1-90]. This is important when we take into consideration
that an average of 12.5 years is required for development of new drugs [38]. Top
pharmaceutical companies, to bring each drug to market, spend an estimated 2
billion USD.
Drug discovery aims at identifying hits and leads that interact with biological
targets such as enzymes, proteins, transmembrane receptors and ion channels.
Notwithstanding, there are not sufficient chemical drugs discovered yearly. This
led to the introduction of virtual screening/docking techniques for faster
identification of hit leads. High throughput virtual screening (HTVS) methods can
filter out unpromising compounds.
The docking and screening methods are efficient but have inherent limitations.
The accuracy of structures is being improved (involving flexibility, solvation,
scoring functions, binding affinity prediction, configuration entropy and
conformational space sampling among other issues). There are still many
challenges,
In order to speed-up and guide the development of new active compounds,
computer-aided drug design projects (docking, virtual screening) have been used.
Effectively, chemoinformatics and computational chemistry are in full bloom due
to their ability to guide the selection of new hit compounds.
Introduced in the late 1990s, virtual screening describes the identification of novel
bioactive compounds using models/computational algorithms/analysis of chemical
data. HTVS (high throughput virtual screening) approaches are used to find novel
hit compounds that can bind to a biological target
via
analysis of large libraries of
chemical structures. Pharmacophore, similarity and fingerprint scanning are
among the models incorporated into HTVS.
The method is also fuelled by increasing available high-quality crystallographic
structures as well as experimental protein-ligand interactions data. Extremely
useful is the screening of large databases of reveals. These are already existing
molecular databases whereas the hit compounds can be purchased directly for
