HASL 4.10S Manual: Chapter 4S

The Graphical Interface

HASL Menubar

The HASL menubar is found under"eslc" on the main Sybyl Menubar. It contains functions that have to do with creating, verifying, testing and visually examining HASL models. The first step in preparing for HASL is the Spreadsheet function, HASLMODEL: Add Column, however.

HASL Menubar Commands

Found as HASL under "eslc". The available commands are Create HASL Model..., Verify HASL Model (Crossvalidation)..., Predict Molecule Activity... and Make HASL Contour Field...

Create HASL Model...

With this command the user chooses the Molecular Spreadsheet rows to be included in the HASL model, identifies the "activity" and HASL columns and selects computational parameters associated with the iteration process. The user can also view the model setup corresponding to the HASL column in the MSS. The results can be written to the MSS if desired. This command allows a Sybyl NetBatch processing option.

View Create HASL Model Dialog Box

Examine HASL Setup...

The Examine HASL Setup dialog is called from several of the top level menubar commands. Its purpose is to allow review of the current HASL parameters. From this dialog the user can also review the current values of the H-VAL paramster set.

View Examine HASL Setup Dialog

Verify HASL Model (Crossvalidation)...

This command is essentially the same as the Create HASL Model... command except that it performs a cross-validation model building exercise. In effect the molecules (rows) selected are each predicted using models constructed from all other molecules (for Leave-One-Out) or large subsets of the data set. This can be very slow for large data sets, especially for Leave-One-Out, because as many models are created and iterated as groups.

View Verify HASL Model (Crossvalidation) Dialog

Predict Molecule Activity...

View Predict Molecule Activity Dialog

Once a (non-crossvalidated) HASL model has been obtained, molecules outside the learning set can be analyzed and their activity predicted. This command will operate either on discrete molecules currently in Sybyl Molecular areas or spreadsheet molecules (whose rows are selected). In the latter case the predictions can be saved in the MSS.

Make HASL Contour Field...

This command converts the HASL model into contourable map files highlighting the types of features selected in the dialog. For example, selecting H-Val .eq. 0 will create a map contour file of spatially-resolved partial activity where the H-Val is zero representing, for the most part, hydrophobic regions.

View Make HASL Contour Field Dialog

Map Contour...

The Map Contour Dialog Box is a convenience utility for contouring and displaying SYBYL (.cnt) contour files.

View Map Contour Dialog

MCP-> Create MCP Database/MSS...

This command aids in creating a database and Molecular SpreadSheet suitable for use with the Multi-Conformer Protocol. The general idea is that molecules from a variety of databases, e.g., conformers of ligands, can be combined into a single database.

View Create MCP Database/MSS

MCP-> Run Multi-Conformer Protocol...

This command executes the Multi-Conformer Protocol. The dialog assists in selecting certain calculational parameters and convergence criteria. The MCP can actually take an extended period to run, on the order of hours to days, so selection of appropriate parameters is important.

View HASL MCP Dialog

MCP-> Analyze MCP Results...

This command tabulates and analyzes tne MCP results file. The object of the analysis is to identify the best performing, from the MCP models, conformer for each ligand. This would presumably give a superior 3D superposition and 3D QSAR model using HASL.

View Analyze MCP Results

Force Ligands & Freeze Conformers

This dialog allows the selection of ligands that are "forced" to be in each MCP model, and also allows a particular conformer of those ligands to be "frozen", i.e., always used and not optimized.

View Force Ligands & Freeze Conformers Dialog...

HASL and the Molecular Spreadsheet

The most important setup and parameter definition functions are handled through the main HASL dialog which is obtained as a column type on the Spreadsheet AutoFill menu.

HASLMODEL: Add Column Dialog Box

This dialog is the main HASL access point. All HASL studies must start with a Sybyl Molecular Spreadsheet that has the relevant molecules in rows and their known biological activity in a column. With this command the user chooses how each molecule in the learning set is to be parameterized for the calculation of the individual molecular lattices. The number of lattice points for each molecule is stored as the HASL column in the MSS, but the actual lattice data is saved in scratch files. The user can choose the type of H-Val data for the model and the dimensions and resolution of the model lattice. It is important to choose a unique identifier for the HASL Model File. This is used thoughout the procedure to identify the current model and data.

View Add Column (HASL) Dialog Box

Edit Basic HASL H-Val Parameters Dialog Box

This dialog allows editing the specific values of the Basic H-Val set of parameters. Note that these are closely related to Sybyl atom types. The suffix :n refers to united atoms with n attached hydrogens. The user can recall either his personal or the program default H-Val paramsters through this dialog. Also the user can save the current set as his personal default.

View Edit Basic HASL H-Val Parameters Dialog Box

Edit Advanced HASL H-Val Parameters Dialog Box

This dialog is similar to the Basic dialog (above) with a few additions. Now, any integer value can be manually entered as a H-Val and there is the possibility of two H-Vals per atom type. Note, however, that a blank is NOT the same as zero.

View Edit Advanced HASL H-Val Parameters Dialog Box

HINT Parameters for HASL Dialog Box

This dialog assigns simple parameters for the use of HINT hydrophobic atom constants as the H-Val definition.

View HINT Parameters for HASL Dialog Box

EState Parameters for HASL Dialog Box

This dialog assigns simple parameters for the use of Molconn-Z E-State atom constants as the H-Val definition.

View EState Parameters for HASL Dialog Box

Calculate SYBYL Region Automatically Dialog Box

This dialog box is called from the main HASL dialog and is used to set the parameters for defining the SYBYL region based on the union space spanned by the entire molecule set. The routine determines the spatial extents of each molecule and creates a region that encompasses all molecules.

View Calculate SYBYL Region Automatically Dialog Box

Define SYBYL Region Dialog Box

The Define SYBYL Region Dialog Box is used if the cartesian coordinate set defining the region (Lower Box Corner, Upper Box Corner) is known, or if a custom region that includes more than one Box is needed. This latter case may be a useful option for some HASL experiments where much of the molecular structures are identical and a "closeup" on the areas of difference is appropriate.