GUELPH, Ontario ¿ Computer-aided drug design holds the promise of producing therapeutically active molecules more efficiently than the traditional compound library synthesis and screen methodologies. However, not every computational drug design technology is created equal.

Barbara Fanning, director of business development at Nanodesign Inc., told BioWorld International the company is enhancing and accelerating the drug discovery and development process through application of their Evolutionary Molecular Design (EMD) technology.

EMD represents a major improvement over existing methods of drug design, such as structure-based design, combinatorial chemistry, computational methods and traditional medicinal chemistry, because it utilizes simulated evolutionary processes to solve complex problems of drug design and optimization. EMD uses information about the structure and biological activity of known pharmacologically active compounds as criteria to rapidly generate new structures that share and improve upon the properties of the original compounds. The objective of the EMD process is to develop novel compounds with a high probability of targeted biological activity, Fanning said.

The design process begins with the construction of virtual receptors that can identify the structural features of ligands that are required for binding with specific biological receptors. Virtual receptors are created through an iterative process using structural and biological activity data from known and inactive compounds.

Virtual receptors can be used to test novel compounds for binding affinity, reducing the need for costly and time-consuming synthesis and biological screening. More importantly, as virtual receptors are constructed, features that are essential for high affinity binding are identified. During construction, physicochemical properties and synthetic feasibility are estimated computationally for each intermediate structure. The conformational stability of each structure is also evaluated.

These parameters are used in combination with testing against virtual receptors to calculate a fitness score during the evolution of the design. Then, the selected compound designs are available for synthesis, testing and further commercial development.

Using EMD, Nanodesign has completed the design and synthesis of new chemical classes of orally available anti-estrogens for the treatment of breast cancer, Fanning said.