plexus design to facilitate structure-based drug design · marvin live to facilitate...
TRANSCRIPT
MARVIN LIVE TO FACILITATE STRUCTURE-BASED DRUG DESIGN
FREDRIK RAHM & JENNY VIKLUND
BETTER MOLECULES – FASTER
A key challenge
in preclinical drug discovery
SPRINT BIOSCIENCE
Reduce tumor
growth
Treat
cancerSelect
target
Find hits Medicinal
chemistry
Make
TestAnalyze
Design
DRIVING MEDICINAL CHEMISTRY PLANS
Better
molecules
faster
IDEA TO DESIGN TO TARGET MOLECULE
Hypothesis
How can we increase
binding affinity?
Evaluate
What models to use?
Models available to whom?
What molecules to actually make?
Populate
What structures to look at?
Marvin Live
Plexus Design
…
Check your ideaand make more
Access to the 3D worldfor everyone
HOW TO MAKE BETTER IDEAS – FASTER?
Improve workflow when sharing, documenting and
evaluating ideas
Scaffold hopping?
Can phenyl reach the selectivity pocket?
Compare with this!
IDEAS RESULTS
Model for predicting potency
I will synthesize the
idea with highest
predicted potency.
BETTER IDEAS BETTER RESULTS
I will synthesize the
idea with highest
predicted potency.
Model for predicting potency
MORE IDEAS BETTER AND FASTER RESULTS
I’ll synthesize the
FASTEST out of
these ideas
Model for predicting potency
HOW TO CREATE MORE & BETTER
IDEAS?
IDEA GENERATION VIA MARVIN LIVE
Sd-file
+ppt
#2 - With this core - can the phenyl
reach the selectivity pocket?
IDEA ANALYSIS
#2 - With this core - can
the phenyl reach the
selectivity pocket?
report
Sd-
file
IDEA GENERATION PART 2
#4 - Does the phenyl fit as an
amide isostere? Bad
alignment in Marvin Live but
please double check?
reference
WHY BETTER AND FASTER?
BETTER
Writing the hypothesis
helps define the question
and finding the answer
FASTER
Quick to evaluate the ideas
• sd-file
• report
More ideas creates
synthetic choice
Nice fit!
Continuing
working on this…
ENHANCEMENT SUGGESTIONS
Better alignments Surface and all-atom rendering of the
protein
Ability to use several alignments
simultaneously
Check your ideaand make more
Access to the 3D worldfor everyone
HOW TO MAKE BETTER IDEAS – FASTER?
Improve workflow when sharing, documenting and
evaluating ideas#
Scaffold hopping?
Can phenyl reach the selectivity pocket?
Compare with this!
# We still like ideas scribbled down on Post-it notes!
