Tutorial

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In this tutorial you perform several Molconn-Z calculations designed to acquaint you with the most commonly used features and calculation strategies of Molconn-Z in its Sybyl-interfaced implementation.

In Lesson 1, you calculate a suite of topological, shape, and electronic descriptors for several small molecules (individually) using SYBYL .mol2 files. The output is a "structure" report that summarizes, in a very readable way, the type of structural and electronic information availabale from the Molconn-Z program. These parameters have historically been key for drug design and QSAR (Quantitative Structure Activity Relationships.

The topics covered in Lesson 1 are:

• Reading in small molecule SYBYL .mol2 files.
• Setting desired Molconn-Z calculation parameters.
• Performing the Molconn-Z calculation.

Lesson 2 illustrates how to calculate and display three-dimensional electrotopological contour maps for small molecules.

The topics covered in Lesson 2 are:

• Setting up parameters for a EStateMap Molecule calculation.
• Performing the EStateMap calculation.
• Display and interpretation of EStateMap contours.

In Lesson 3, you will model a data set of halocarbons against anaesthetic potency and LD₅₀ with the Molconn-Z suite of parameters. In fact a very nice model can be obtained from this data set with conventional 1-D QSAR descriptors. Also included in this model are the new Atom-type EState descriptors. The topics covered in Lesson 3 are:

• Creating a Sybyl Molecular Spreadsheet (MSS) from a pre-supplied Sybyl molecular database (.mdb)
• Entering the biological data for AD₅₀ and LD₅₀ into the MSS.
• Selecting an appropriate set of descriptors to use in the PLS regression.
• Examining the resulting model.

Lesson 4 demonstrates using EState fields in 3D QSAR (CoMFA). In this lesson the standard CoMFA training data for steroids will be examined with the EState and HEState fields instead of the steric and electrostatic fields of standard CoMFA.

The topics covered in Lesson 4 are:

• Using Molconn-Z to fill a QSAR table column with an electrotopological stste field similar to the standard CoMFA electrostatic and steric fields.
• Analyzing 3D QSAR results with contour maps.