Scoring profile

In the case of data following a trilinear model structure [7], the profiles in the score matrices X in Xaug of (10) will present the same shape in the score profiles (or, in other words, the relative distribution of contamination patterns among samples in the different data matrices is the same) in the different individual data matrices D (obtained in the different sampling campaigns). In this case, the data set fulfills the trilinear model [7, 15, 21], which can be described by (11) (in this equation, superindex t in D k and X k matrices indicates that they conform to the trilinear model) ... 

The most commonly adopted approach is to rank compounds according to the total number of alerts. If molecules are to be prioritized with respect to properties such as permeability, solubility, and so forth, the goal is to find the best compromise between these continuous parameters. For this purpose, each property is scored by assigning a dimensionless scale di between zero ( criterion not met ) and one ( target achieved ), with intermediate values being obtained by interpolation between the minimum and maximum for each property. The score profile for each compound is summarized into an overall desirability D by calculating the geometric mean of the individual dt values [67, 68] ... 

Figure 3 Score profiles for cxlbjarde (Figure 3A) and for cox3 parde (Figure 3B) of cytochrome oxidase from Paracoccus denitrificans [14] are obtained by substraction of turn preferences from a-helix preferences (full line). Digital predictions, as outcome of the best training procedure for the SPLIT algorithm with Kyte-Doolittle hydropathy scale (Methods), are shown as bold horizontal bars at the score level 0.5. Observed location of TMH segments are shown as bold horizontal bars at the score level 0.2.

Figure 4 Score profiles for porin from Rhodobacter capsulatus are obtained by subtraction of turn preferences from helical preferences (full line) and as sum of P-sheet preferences and hydrophobic moment scores for assumed p-sheet conformation (dotted line). Kyte-Doolittle scale [17] is used to calculate preferences, while PRIFT scale [50] is used to calculate hydrophobic moments. Observed transmembrane strands are shown as bold horizontal bars at the score level 2.0.

In the probabilistic scoring approach, a scoring profile is defined to reflect the profile of properties required for an ideal compound in the context of a project (an example is shown in Figure 8.11). This profile may include simple calculated characteristics, predicted properties, or experimental endpoints. Underlying each of the property criteria is a desirability function that defines the importance of the property to the overall objective of the project and the acceptable compromises. These desirability functions are defined in terms of the impact of the property on the chance of success of the compound a low desirability indicates a low chance of success, or equivalently a high risk, due to the value of the property. Thus, the overall score will reflect the best estimate of the overall chance of success of a compound. As a probability, the overall score will be between zero and one and is multiplicative with respect to the contributions of the individual properties. 

FIGURE 8.11 Example of a scoring profile. This defines the properties of interest, the ideal desired values, and relative importance of each property. Underlying each criterion is a desirability function, an example of which is shown for log P. For color details, please see color plate section. 

Fig. 15.4 Docking results Typical score profile predicted by docking to 300 snapshots periodically extracted from several simulations of influenza neuraminidase over 30 ns sampling time for a zanamivir and b compound 2, known to bind the open conformation of influenza neuraminidase. The histogram visualizations (c, d) show that best scoring values are obtained with conformations from the ligand-bound simulation. Docking poses (6/acA ) discussed in the text are shown in comparison with native poses of zanamivir green) and compound 2 blue) (e-g)...

Figure 15.5 Scoring profile for selection of compounds intended for an orally administered drug against a peripheral target, based on predicted ADME and physicochemical properties. A desired criterion is defined for...

Figure 15.7 Property profiles and score plots for series 8,11, and 13, derived from the screening library Illustrated In Figure 15.6. The property profiles (top) show the percentage of compounds In the series that meet each property criteria In the scoring profile shown In Figure 15.5 (the bars are In the same order as the properties In the profile). The score plots...

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