Multi-Parameter Optimization (MPO) Scoring Panel

Choose properties for multi-parameter optimization of a property set, and set weights for each property and property ranges for classification of values as good, marginal, or bad. The changes are reflected immediately in the MPO diagram and related scores in the Ligand Designer Panel.

To open this panel, click the Edit button in the Multi-Parameter Optimization section of the Ligand Designer Panel.

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Overview of Multi-Parameter Optimization (MPO) Scoring

The multi-parameter optimization (MPO) scores a set of property values individually and combines them to produce an overall score. Each property is mapped to a set of values between 0 and 1 with the use of a logistic curve (or Fermi function), 1/(1+exp(X)), so that all properties are on the same scale. The logistic curve is determined from two thresholds that divide the property range into "good" values, "marginal" values, and "bad" values. These two values are used to determine X, where X = a(x-b) and x is the original property value variable, given that the values of the logistic curve at the two thresholds are 0.2 and 0.8, with the range in between representing the marginal values. The properties are classified according to whether the desirable values are at the low end of the property range, the high end, or in the middle. For low desirable values, X is reversed, X = a(b-x), so that values above 0.8 represent the desirable values. For desirable values in the middle, two logistic curves are required and hence four thresholds.

For each ligand, the property values are calculated and converted into a normalized score. The overall score is calculated by taking the weighted geometric mean of the normalized scores. The geometric mean is used rather than the arithmetic mean to ensure that one bad value is not underrepresented in the MPO score.

Multi-Parameter Optimization (MPO) Scoring Panel Features

Property table

This table lists the properties and related settings in the current MPO scoring profile. You can edit the table to customize the profile. As you change the values, the MPO score and diagram are updated in the Ligand Designer Panel. The thresholds must always be in ascending order of property value: Threshold 1 < Threshold 2 < Threshold 3 < Threshold 4. You can use the check box in the first column to include or excluded properties in the scoring function. You can also select rows in the table.

Property Property name
Importance Ranking of the property in the scoring function. The importance index (1 - 5 with larger more important) is used as the weight value for the property when the weighted geometric mean is taken to determine the MPO score.
Value Distribution This classification indicates where the desirable ("good") values fall in the range of property values: on the low end (Lower Better), in the middle (Middle Good) or on the high end (Higher Better).
Threshold 1 Cutoff between bad (lower) and marginal (higher) values for Higher Better and Middle Good distributions, or between good (lower) and marginal (higher) values for Lower Better.
Threshold 2 Cutoff between marginal (lower) and good (higher) values for Higher Better and Middle Good distributions , or between marginal (lower) and good (higher) values for Lower Better.
Threshold 3 Cutoff between good (lower) and marginal (higher) values for Middle Good distributions at the higher end of the value range.
Threshold 4 Cutoff between marginal (lower) and bad (higher) values for Middle Good distributions at the higher end of the value range.
Unselect All button

Clear the checkboxes for selection of the properties in the property table.

Add Project Table Properties button

Select a property to add to the scoring profile. Opens a standard Choose Property dialog box, where you can select a single property to add. The properties listed are those that are available in the ligand set in the Ligand Designer. When you click select, the dialog box closes and the property table is updated with the new property, and the Scoring function is set to Custom.

Delete button

Delete the Project Table properties (rows) that are selected in the table. You cannot delete the standard properties.

Scoring function option menu

Choose a preset MPO scoring profile, from a list of common filters (such as Lipinski, the default). The table is populated with the properties and value settings for the selected scoring profile, and the MPO figure in the Ligand Designer Panel is updated.

If you add properties to the table, or edit any of the values, the scoring function is switched to Custom.

Reset button

Reset the panel to its default settings, clearing all changes.

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