Figure 4

Visual summary of the results of canonical correlation between the MAF and PocketPicker descriptor matrices. A. Three statistically significant canonical factor pairs were obtained with the correlation values of 0.87, 0.84 and 0.77, respectively. Canonical correlation (R value) for each factor pair is shown in the middle part. Representative molecules for the MAF factors are shown on the left panel (orange and blue background for positive and negative salients, respectively). Distribution of PocketPicker salients is shown on the right panel. The six different buriedness levels are represented by the letters A-F, with F representing the highest level of buriedness while distance parameters were collected into three groups (1-7 Å, 8-14 Å, 15-20 Å). Orange and blue colors stand for the positive and negative salients, respectively. White blocks represent the absence of a given descriptor pair within a given distance. See text for the details. Abbreviations: BZDs: benzodiazepines; Morph.: morphine derivatives; Barb.: barbiturates; PPIs: proton pump inhibitors; Phen: phenotiazines; TCAs: tricyclic antidepressants. B. Shapes of protein binding pockets represented with high scores among the first three canonical factor pairs. Positive and negative salients are represented by orange and blue boxes. Binding site shapes are represented with colored balls positioned in a 1Å-spaced grid with deeper blue representing a higher level of buriedness. Protein surfaces were removed for better view of the binding pockets in most cases excluding flat, surface sites e.g. 2pk4. Proteins of the positive salients of factor III have narrow, deep binding pockets while negative salients contain shallow, small pockets (1aj6, 1apy) and wide, extensive binding sites (2fvv, 3fap). Factor II proteins can be described as having binding sites of medium size and width. Based on the distribution of salient loadings of PocketPicker variables, factor I proteins do not form a coherent group. Elongated (1d3g), branching (1zsx, 2p0a) and bulky binding sites (2cca) belong to this factor.