RACHEL^TM stands for:

• RACHEL - combinatorial derivatization of user-specified sites to enhance lead refinement.
• Component database generation, registration, and management.
• Automated generation of scoring functions based on user supplied ligand and receptor data.
• Advanced conformational search engine capable of sampling nearly 1x10⁶ conformers per second.
• User defined Markush-like building descriptors to direct the generation of structures.
• Heuristic component selection and diversity metrics to accelerate the generation of solutions while ensuring maximum component diversity.

Here we see an example of RACHEL's implementation.  This lead compound contains a stable, tight-binding region (black), and a phenyl ring that should be replaced to improve receptor complementarity  (red).  RACHEL requires the attachment point of the weak-binding portion as input.  She then removes the offending ligand region and uses the attachment point to create a population of derivatives by adding, deleting, and substituting fragments chosen from the component database  (green) to fill the active site.  The binding energies of the resulting derivative ligands are then calculated.  Those structures that augment binding are retained while those that do not are discarded.  This process repeats as the new population of structures is then processed to generate the next round of derivatives. By making incremental changes iteratively, these programs generate a set of ligands with improved receptor complementarity over time.  As stated above, RACHEL possesses numerous features that truly separate her from any other ligand design software.
 

To see real-world examples of RACHEL's utility, please click here.

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