Selection GOLPE

The variable selection methods have been also adopted for region selection in the area of 3D QSAR. For example, GOLPE [31] was developed with chemometric principles and q2-GRS [32] was developed based on independent CoMFA analyses of small areas of near-molecular space to address the issue of optimal region selection in CoMFA analysis. Both of these methods have been shown to improve the QSAR models compared to original CoMFA technique. 

Cruciani, G. and Watson, K.A. Comparative molecular field analysis using GRID force-field and GOLPE variable selection methods in a study of inhibitors of glycogen phosphorylase b. 

Cmciani, G., Watson, K. Comparative Molecular Field Analysis Using GRID Force Field and GOLPE Variable Selection Methods in a Study of Inhibitors of... 

To further validate the GRID/GOLPE model it was necessary to test its predictiv-ity for external test sets. We carefully checked the literature for further ER data sets, which were experimentally tested in the same assay under the same conditions [67-70], In order to test the general predictivity 36 structurally diverse ER ligands were selected from the mentioned studies (examples are shown in Fig. 7.3, the whole data set is described in detail in [36]). 

Moreover GRID can be used to understand the structural differences related to enzyme selectivity, a fundamental field in the rational design of drugs. GRID maps can also be used as descriptor input in statistical procedures like CoMFA, GOLPE or SIMCA for QSAR or 3D-QSAR analyses. 

Among these methods, Generating Optimal Linear PLS Estimations (GOLPE) is a variable selection method for selecting by -> experimental design a limited number of - interaction energy values, aimed at obtaining the best predictive PLS models. 

In order to optimise the in vitro profile, we focused our attention on the nature of the substituent at N-1 and a quantitative structure-activity study was performed on a series of N-1 alkyl derivatives. After selection of variables, the affinity for the CCK-B receptor was related to the calculated values of both lipophilicity [26] and molar refractivity [27] of the substituent and the following equation was derived using PLS analysis implemented in program GOLPE [28] (all parameters are referred to the substituents at N-1) ... 

Generating Optimal Linear PLS Estimations = GOLPE variable selection > genetic algorithm - variable subset selection variable selection... 

Asikainen, A.H., Ruuskanen, J. and Tuppurainen, K.A. (2005) Alternative QSAR models for selected estradiol and cytochrome P450 ligands comparison between classical, spectroscopic, CoMFA and GRID/GOLPE methods. SAR ej QSAR Environ. Res., 16, 555-565. 

Cruciani, G., Clementi, S. and Pastor, M. (1998) GOLPE-guided region selection, in 3D QSAR in Drug Design, Vol. 3 (eds H. Kubinyi, G. Folkers and Y.C. Martin), Kluwer/ESCOM, Dordrecht,... 

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