CoMFA fields

Depending on the selected probe and the defined potential energy function, several molecular interaction fields can be calculated. The most common are steric fields and electrostatic fields, sometimes referred as CoMFA fields because originally implemented in CoMFA. Several interaction fields are actually calculated in the - GRID method. 

Autocorrelation coefficients are also calculated on the basis of three-dimensional molecular interaction fields (e.g., MIP, CoMFA field or CoMSIA field). These fields are generated by mapping of atom properties to the spatial neighborhood of the molecule [23]. Distances between grid points located in the space around the molecules are used as input for the autocorrelation algorithm. 

TV =48), and a seven-PLS-component model was reported for arAR, with a 0.6 contribution from electrostatic fields (N = 42). This difference can be traced back to the 10 compounds removed from the initial data set while using the MCS alignment, but the models were perhaps overfitted in this particular case. We further notice that the electrostatic CoMFA field contributions (Table 5), 0.63 for 5HT1A, and 0.66 for arAR, respectively, are in qualitative agreement with the previously reported higher component models [128]. Based on the comparative QSAR approach, the two- or three-PLS component models are warranted for both 5HT1A and arAR in this data set. 

Figure 15 Comparison of stdev coeff CoMFA fields for CoMFA models derived on 5-HTia activity (compound numbers as in Fig. 12). Electrostatic fields are on the left, steric fields on the right. (See color plate at end of chapter.)...

CoMFA fields were also proposed and used to derive new steric and electronic parameters for classical QSAR studies [38, 1018]. 

Here S is the solvent-accessible surface area for atom /, a, is the hydrophobic atom constant for atom /, and R , = e, where r is the distance between atom i and grid point t. In addition to supplementing standard CoMFA fields, HINT has been demonstrated to effectively model experimentally determined log P values in cases where CLOGP values fail. A different fragment-based, distance-dependent method to estimate lipophilicity, the molecular lipophilic potential (MLP), has been recently shown to be useful in docking and as a third field in CoMFA studies. 

First formulated by Pearson in 1901, PCA was outlined by Fisher and MacKenzie in 1923 and by H. Wold in 1966, who discovered the NIPALS algorithm (see Wold and references therein). PCA is also called factorial analysis (FA), single-value decomposition (SVD, which is the full PCA), or Karhunen-Loewe expansion (KLE). Data reduction by PCA is of key importance in CoMFA because it allows large amounts of data to be approximated by a small mathematical structure. In PCA, the X matrix of a given training set (e.g., a CoMFA field) is assumed to include a model and noise (the part of the data that cannot be explained by the model). The X matrix is thus a combination of the principal component model matrix M and the noise matrix E ... 

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