CoMFA Results

A beneficial lattice point corresponding to increasing Y has either  

CoMFA fields give information about receptor binding sites. That is, they give localized information complementary to the receptor with respect to the current alignment. We use the term localized information because there is no 

If increasing Y is desired, then negative S P values are detrimental for Y. In regions where positive S values and negative P values are associated, steric bulk should not be present it is possible that the receptor has atoms occupying 

For both steric and electrostatic fields, especially the latter, regions of interest are the high contribution stdev p fields. Cross-examination of negative P coefficients with molecular fields should be undertaken only where highly (in)active compounds have fields that disagree with the average CoMFA field. 

Central to the goals of QSAR modeling is the ability to evaluate (predict) new chemical structures, in an effort to prioritize the synthesis of new ligands. To test the predictivity of QSARs, the model is evaluated using an external 

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Chart 14 Essential regions responsible for epothilone activity on the structure of epothilone B, according to CoMFA results of Lee and Briggs [108]... 

T.I. Opera et al., 3D-QSAR of human immunodeficiency virus (I) protease inhibitors. III. Interpretation of CoMFA results. Drug Des. Discov. 12, 29-51 (1994)... 

CoMFA results peak at three PLS components for 5FfT1A, in agreement with ALMOND after FFD selection (Table 7). A one-component and a four-component model for D2 antagonism are illustrated for CoMFA with respect to cross-validated predictivity (see Figs. 13 and 14). Both plots indicate a clear separation between active... 

CoMFA results are difficult to compare with each other because of the different fields, box sizes, and other options. In addition to this, prior CoMFA versions (up to 5.4) contained an error in the calculation of the electrostatic fields [1012]. Autoscaling of variables should be avoided PLS analysis may produce wrong results if individual grid points largely reduce their variance in the cross-validation, which seemingly occurs quite often [1013] in the CoMFA cross-validation wrong... 

The CoMFA methodology was also used to describe nonlinear lipophilicity-activity relationships, c.g. the inhibitory activities of quaternary alkylbenzyl-dimethylammonium compounds vs. Clostridium welchii (eqs. 206—208) [1025], other antibacterial and hemolytic activities [1026, 1027], and toxic activities of alkanes in mice (eqs. 209-211) [1026] the results of classical QSAR studies (eqs. 206, 207, 209, and 210) [23, 440] were compared with the corresponding CoMFA results (eqs. 208 and 211) [1025-1027] only homologous series of compounds were investigated. 

Data set Complete matrix GOLPE Reduced Matrix CoMFA Results ... 

Generally, the open-chain neonicotinoids are less lipophilic than the corresponding neonicotinoids with a ring structure (Chapters 29.2.2 and 29.2.3). Based on CoMFA results, a binding model for imidacloprid (11) has been described. 

We have analyzed the nature of the dye-fiber interaction for 27 disperse azo dyes by means of several QSAR methodsbased on the pharmacophore theory of dye-fiber interaction. Hydrophobic effects were excluded because CLOGP gave a limited correlation, = 0.32. MTD (r = 0.924) and CoMFA (j-2 = 0.925 and = 0.776, LOO) results emphasized the importance of steric contributions for enhancing the affinity to cellulose fiber. CoMFA results apparently confirm the validity erf the pharmacophore theory of dye-fiber interaction. This was not surprising because similar results between CoMFA and MTD were reported in 1993. ... 

T. 1. Oprea, C. L. Waller, and G. R. Marshall, Drug Design Discovery, 12, 29 (1994). 3D-QSAR of Human Immunodeficiency Virus (I) Protease Inhibitors. III. Interpretation of CoMFA Results. 

When added to CoMFA, the MLP is calculated by Eq. [33] in the same 3D grid as the steric and electrostatic fields. However, the inclusion of MLP in CoMFA is not straightforward because of the composite nature of lipophilicity, which as discussed earlier contains a hydrophobic component and polar terms. In contrast to 2D-QSAR, where the correlation between explanatory variables is easy to assess with a correlation matrix, the correlation between CoMFA signals associated with each molecular field is far from evident. At present, a systematic comparison of all CoMFA models generated by all possible combinations of molecular fields is the only reliable means of detecting correlations between CoMFA results. ... 

Recommendations for CoMFA studies and 3D QSAR publications have been defined. These recommendations should help to avoid the most common errors and pitfalls and should ease the reproduction of CoMFA results by other scientists in a short version they are summarized below. 

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