RACHELTM stands for:





Enhancement of

Lead compounds

She is an all-purpose ligand refinement software package designed to combinatorially derivatize a lead compound to improve ligand-receptor binding and accelerate drug discovery.

RACHEL encompasses numerous features designed to work cohesively in this endeavor.



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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