Now the power of 3D-QSAR predictions are available in a new search engine that can address millions of compounds for those likely to be pharmaceutically active.

For years 3D-QSAR techniques like CoMFA®* have been used to produce predictive models of biological activity. CoMFA® models are based of the molecular fields of a small set of active molecules. These fields, including electrostatic, steric, hydrogen-bonding and hydrophobic interactions, are used as the predictor variables in a statistical treatment such as Partial Least Squares (PLS). PLS chooses unique combinations of the predictor variables that best predict the biological activity.

3D-QSAR models can predict the activity of new compounds very well. However, these predictive models can not be applied to large databases of compounds. Before the activity of a compound can be predicted, the correct conformation of the 3D structure must be chosen and it must be aligned with the training set compounds. This process is tedious and error-prone, and is often done manually. This precludes the use of the predictive model to select compounds from large databases. 3DQS addresses this problem.

3DQS converts the 3D-QSAR model into a 3D molecular field query of the type used in ChemNavigator's patented derivative field based search technology applied in 3DPL. This allows databases of many millions of compounds to be searched for those that give good 3D-QSAR predictions. The conformation and alignment of the database structures is adjusted automatically by 3DQS "on-the-fly" to give the best predicted activity. 3DQS has major advantages that allow for rapid identification of potential active molecules:

• No Knowledge of protein target required: 3DQS is designed to develop a predictive biological model based on entering known biologically active compounds as input. No knowledge of the target protein is necessary.
• Provides a strategy for the application of existing CoMFA® models: 3DQS can use the aligned molecule sets from existing Comparative Molecular Field Analysis (CoMFA®)
• Speed enables in silico screening of millions of small molecules: Running on a single 1.4GHz server, 3DQS is able to evaluate over 10 million chemical structures in less than 4 days. Much larger structure sets can be run, which eliminates the need to filter out large numbers of potentially valuable samples before the virtual screening experiment.

Contact us at ChemNavigator if you would like to become an early tester of this new 3D search system.