Ligand Design Examples
Using
RACHELä and CHARLIEä
What Separates RACHEL from
everybody else?
Why?
Disclaimer – Following
Examples
RACHEL Combi-Chem Example
Defining Anchor Bond
Defining Target Atom
Defining Target Atom
Steric Characterization of
Active Site
Steric Characterization of
Active Site
Critical Ligand Receptor
Interactions
RACHEL Chemical Template
Defined Component #1
Wildcard Component
Defined Component #2
Defined Component #3
Running the RACHEL Search
Results (Hits)
Results (Hits)
Results (Hits)
Results (Hits)
Slide 22
RACHEL Combi-Chem Example
Scytalone Dehydratase is a
molecular target of inhibitor design efforts at preventing the fungal disease
caused by Magnaporthe grisea.
Steric environment within
Scytalone Dehydratase active site
Potential Electrostatic
Interactions to Exploit
RACHEL Chemical Template
RACHEL Chemical Template
Scytalone Dehydratase:
Target Function
Results (Hits)
Results (Hits)
Results (Hits)
Results (Hits)
Slide 34
RACHEL Combi-Chem Example
CML: chronic myelogenous
leukemia
STI-571 “Head
region”
Steric Enclosure
Potential Electrostatic
Interactions to Exploit
RACHEL Chemical Template
STI-571 Dehydratase: Target
Function
Results (Hits)
STI-571 “Tail
region”
Electrostatic box
RACHEL Chemical Template
RACHEL Chemical Template
Results (Hits)
Results (Hits)
Results (Hits)
Results (Hits)
Slide 49
CHARLIE Example: SAR by NMR
CHARLIE Chemical Template
Results (Hits)
Slide 53
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