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
features that truly separate her from any other
To see real-world examples of RACHEL's utility, please click here.
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