Catalyst HypoGen

Accelrys, http //www.accelrys.com/sup-port /life/catalyst/hypogen.html. 

If one compares Catalyst-HipHop with Catalyst-HypoGen, for instance, it is common to obtain very different models. Since HipHop searches common features amongst active molecules, the output models may have retained features that HypoGen may have discarded as not being relevant to explain activity. The example that we will detail at the end of this chapter is a good illustration of this. It is worth mentioning that this is due to the input dataset and that Catalyst provides solutions to circumvent this. 

Some pharmacophore searching programs are designed to provide 3D-QSAR models that are capable of predicting the activity from a quantitative point of view. Apex-3D [34], Catalyst HypoGen [9] and Phase [17] are examples. Consequently, such a model should have correct statistics and abide by the common QSAR validation approaches. Box 3 describes some of them very briefly as they have been reviewed elsewhere (see [35-41]). 

Similarly, the root mean square [RMS) of errors gives an insight into the errors of the prediction. In Catalyst-HypoGen, the RMS is scaled according to the uncertainty of each activity measure (Unc) ... 

Fig. 15.6 (b) Activities of the mGlu4 agonists reported with L-glutamate (l-GIu) as a reference. Molecules used in the training set for Catalyst-HypoGen are flagged with an x . Those taken to plot the ROC curves are flagged either as actives (A) and inactives (I). 

In this case study, the training set elaboration is utterly important because the mGlu4 agonists dataset is amongst the difficult ones (poor activities, inaccurate EC50 values for the least active compounds, poor structural variability, noticeable flexibility of the receptor, etc.). We report here how the training set was built to be used by Catalyst-HypoGen. 

Xiao, Z., Varma, S., Xiao, Y.-D. andTropsha, A. (2004) Modeling of p38 mitogen-activated protein kinase inhibitors using the Catalyst HypoGen and k-nearest neighbor QSAR methods. J. Mol. Graph. Model, 23, 129-138. 

Transporters are the final class of integral membrane proteins that are important as drug targets. Structurally, they are among the most complex receptors known hence, they are ideally suited to analysis via pharmacophore discovery. Catalyst/HypoGen was used in the discovery of a pharmacophore for the Na + /bile acid transporter [61], A... 

Compounds and their conformational models were imported to Catalyst and subjected to the HypoGen routine to build chemical feature-based pharmacophore models using hydrogen bond acceptor lipid (HBA), hydrogen bond donor (HBD), positive ionizable (PI), ring aromatic (RA) and hydrophobic ... 

Urotensin II Aventis in-house (N.R.) HypoGen/Catalyst Ligand-based pharmacophore 918 1.2 11 (400 nM) [53]... 

Methods discussed so far are based on a few known active ligands. Several methods have been developed that attempt to use the activity data when generating the pharmacophore model. The HypoGen module of Catalyst uses a cost func-... 

Fully Automated Pharmacophore Discovery Catalyst s HypoGen, DISCO, Catalyst s Hiphop, DANTE... 

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