Site MetaSite

MetaSite Site of metabolism prediction for CYP2C9 and CYP3A4 and others www.moldiscovery.com... 

Cruciani et al. [92] have developed the program Metasite for the prediction of the site of oxidative metabolism by CYP450 enzymes. Metasite uses GRID molecular interaction fields to fingerprint both structures of CYP450s (from homology models or crystal structures) and test substrates and then matches the fields. Zhou et al. [93] showed that Metasite was able to correctly predict the site(s) of metabolism 78% of the time for 227 CYP3A4 substrates. Caron et al. [94] used Metasite to predict the oxidative metabolism of seven statins. 

A metasite with full and changing MEDLINE search engines List of free sites... 

The evaluation of the impact of the different crystal structures on the prediction of the site of metabolism by the MetaSite methodology without reactivity correction has been considered. In this case one can conclude that overall the rate of good prediction (number of experimentally determined sites of metabolism among the first three solutions predicted by MetaSite) is similar for the different structures. Nevertheless, there is only a moderate overlap between the compounds that are well predicted by each crystal structure, and a combination of all structures usually yield higher prediction rates. When using the reactivity correction, the difference between the prediction rates for each crystal structure is reduced, suggesting a diminishing rate of the crystal structure used for the analysis. 

The overall procedure is called MetaSite (site of metabolism prediction) [32]. The M IF calculations, pharmacophoric recognition, descriptor handling, similarity computation, reactivity computation, inhibition and subselectivity are calculated automatically once the ligand compound(s) is(are) provided. The complete calculation is performed in few seconds in IRIX Linux or Windows environments. 

Finally MIFs will be used to explain cytochrome P450 (CYP) 3A4 inhibition. The use of METASITE in understanding and predicting the site of metabolism... 

There are two main factors that determine the site of metabolism (i) the chemical reactivity and (ii) the preferred orientation of the compound inside the cytochrome cavity. A new technique called MetaSite [32] has been developed in order to consider at the same time, the substrate-cytochrome interaction and the chem-... 

The procedure is called MetaSite (Site of Metabolism prediction) [25]. The MetaSite procedure is fully automated and does not require any user assistance. All the work can be handled and submitted in a batch queue. The molecular interaction fields for CYPs obtained from the GRID package are precomputed and stored inside the software. The semiempirical calculations, phaimacophoric recognition, descriptor handling, similarity computation, and reactivity computation are carried out automatically once the structures of the compounds are provided. The complete calculation is performed in a few seconds in IRIX SGI machines, and is even faster in the Linux or Windows environment. For example, processing a database of 100 compounds, starting from 3D molecular structures, takes about three minutes at full resolution with a... 

Virtual predictions of metabolic (bioactivation) sites in molecules. The in silico tool MetaSite can identify the "most likely" sites of P450-mediated... 

This is a worldwide metasite that contains links to hundreds of chemistry-related sites from companies, research centers, publications, history and education. This is a good site to start a search for chemistry material. 

This is a metasite that contains links to other sites that list lots of chemistry software. 

The most severe drawback of this kind of approach is obvious The Fukui function describes reactivity against an isotropic, abstract reactivity bath . If a drug is positioned in a specific orientation within the active site of a cytochrome, the oxidation will not take place at the same site of the ligand as it would in an isotropic situation (e.g., in solution, with a small, sterically less demanding reaction partner). This is a common drawback of any ligand based approach. Combinations of docking approaches and estimations of reactivity like MetaSite... 

MetaSite has repeatedly proven useful in the optimization of metabolic properties of lead-like compounds [95, 96] (see earlier) and it was used to study potentially labile sites of compound 4 in detail. 

---