[Colloquium] Talk Reminder! Research at TTIC Tomorrow at Noon: Yang Shen

[Dawn Ellis]

When:     Friday, May 31st at Noon

Where:    TTIC, 6045 S Kenwood Avenue, 5th Floor, Room #526

Who:      Yang Shen, Assistant Professor,  TTIC

Title:    Advancing Optimization and Learning for Computer-Aided Drug Design

In this three-part talk, I will present recent efforts that aim at removing
practical hurdles for computer-aided drug design.  The first two parts
center on physically sound and computationally efficient methods that
represent target-protein flexibility for optimization and target-protein
mutability for learning.  And the last part involves a real-world case
study that presents even more challenges.

I will first talk about drug design for a “fixed” target by docking small
molecules into a target protein structure, which can be recast as solving a
free energy minimization problem.  One challenge is that the search space
is extremely high-dimensional when considering protein flexibility.  I will
show that the space can be reduced as a basis set formed by normal modes,
thus optimization can be done efficiently in the reduced space of
rigid-body motion and flexibility.

I will then consider a “moving” target that mutates and becomes resistant
to drugs.  Resistance-mutations often outpace current drug-discovery
processes, especially in infectious disease and cancer treatments.  In
addition, it is unlikely that structures or even sequences of all possible
mutants will be unveiled.  I will show that one can design robust drugs for
even unknown mutants by learning from those designed for an ensemble of
wild-type structures sampled by molecular dynamics.  The results also
indicate that intrinsic protein flexibility could pose similar demands for
robust drugs as protein mutations do.

Lastly, I will briefly describe a recent collaboration combining
experimental and computational efforts to prospectively identify
androgen-receptor mutations that can cause resistance to a newly approved
prostate-cancer drug (enzalutamide), to explore molecular mechanisms
underlying such a resistance-mutation, and to rationally redesign the drug
to overcome the mutation.  This collaboration is with Charles Sawyers
(Memorial Sloan–Kettering Cancer Center) and Geoffrey Greene (University of
Chicago).


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Research at TTIC Seminar Series

TTIC is hosting a weekly seminar series presenting the research currently
underway at the Institute. Every week a different TTIC faculty member will
present their research.  The lectures are intended both for students
seeking research topics and adviser, and for the general TTIC and
University of Chicago communities interested in hearing what their
colleagues are up to.

To receive announcements about the seminar series, please subscribe to the
mailing list: https://groups.google.com/a/ttic.edu/group/talks/subscribe

Speaker details can be found at: http://www.ttic.edu/tticseminar.php.

For additional questions, please contact Nati Srebro at nati at ttic.edu.

-- 
*Dawn Ellis*
Administrative Assistant
773-834-1757
dellis at ttic.edu

TTIC
6045 S. Kenwood Ave.
Chicago, IL. 60637
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