Tutorial
In this tutorial you perform 1) a complete HASL calculation
designed to acquaint you with the calculation strategies of the HASL 3D-QSAR method,
and 2) a "simulated" calculation of the HASL Multi-Conformer Protocol.
In Lesson 1, you create
and verify with cross-validation a HASL model for the Corticosteroid
Binding Globulin (CBG) mesurement of the classic 21 member steroid molecule
set of Cramer et al. (J. Am. Chem. Soc. 1988, 110, 5959-5967.). This data set, which was first introduced
as the test set for CoMFA, can be convincingly modeled with HASL.
The topics covered
in Lesson 1 are:
- Creating a SYBYL Molecular
Spreadsheet (MSS) from a database and activity table.
- Adding a HASLMODEL column
to the MSS.
- Verifying by cross-validation
a HASL model.
- Creating a 3D HASL model
of the steroid data.
- Predicting the Activity
of a new steroid molecule not in the learning set.
- Mapping the HASL model
to visualize the activity profile.
In Lesson 2, you set-up and
initiate a multi-conformer protocol (MCP) analysis of ligands for antithrombin.
There are 28 ligands and each ligand has between 9 and 11 conformers; as an internal
check seven of the ligands have crystal conformations. This data and the MCP
were described in Doweyko, A.M. ...
The topics covered
in Lesson 2 are:
- Creating an MCP molecular database from a
collection of ligand databases and creating a new SYBYL Molecular
Spreadsheet (MSS) from this database.
- Designing and MCP experiment
to effectively sample the ligand and conformer space.
- Monitoring the progress of the
MCP experiment and knowing how and when to stop it.
- Analyzing the accumulated MCP
results in the log file.
- Interpreting the final MCP
Analysis results.