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*    GRAND Seminar
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*    http://cs.gmu.edu/~robotics/Main/GrandSeminar
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   GRAND Seminar: Improving Drug Development by Connecting Medicinal
   Chemistry with Drug Repositioning and Modern Machine Learning Methods

Tuesday, May 01, 2012
12:00pm
ENGR 4201
*Iwona Weidlich*


         Abstract

Developing drug candidates from scratch has turned into a billion-dollar
expense that is not delivering enough profitable products to market.
Novel approaches which merge chemistry with biology and informatics
contribute to the development of selective lifesaving drugs needed by
patients. We implement machine learning classifiers for HTS Data
Analysis, Screening and drug repurposing with high probability of
selecting drug candidates eligible for Phase II of clinical study free
from ADME/Tox-related problems. We used small molecule bioactivity data
for HCV RNA Polymerase to train and test QSAR models and apply these
robust models for compound ranking and hit identification in drug
repositioning techniques. Random Forest and kNN algorithms were used
with Morgan fingerprints of 679 small molecules with curated IC50
values. After filtering various drug-like databases (DrugBank, MDL,
NIAID-NIH, ComGenex) compounds were selected and tested against HCV. We
discuss the challenges in drug repositioning faced in academia,
government and pharmaceutical industry.


         Speaker's Bio

Dr. Weidlich received her Ph.D. in Pharmaceutical Sciences from the
University of Medical Sciences, Poznan, Poland in 2005. Her Ph.D.
research focused on developing anti-cancer agents that are designed to
be activated only inside a cancerous cell but have benign form in the
systemic circulation. Her research interests also include using very
large collections of chemical databases to filter and extract relevant
subsets of molecules for closer analysis, and performing physicochemical
and ADME/Tox property predictions. Specifically, she is interested in
designing and evaluation of novel anti-cancer agents. She joined the
Computer-Aided Drug Design (CADD) group at the Chemical Biology
Laboratory, National Cancer Institute in Frederick, NIH as a
postdoctoral fellow in October 2005. Dr. Weidlich has been conducting in 
silico screening for the inhibitors of cancer DNA, specifically
tyrosyl-DNA phosphodiesterase (Tdp1) and Shc Src homology 2 (SH2)
domain. She designed new, more powerful Tdp1 inhibitors and Shc SH2
domain-binding inhibitors: tetramer peptide-peptoid hybrids exhibiting
up to 40-fold increase in affinity.

-- 
Jyh-Ming Lien
Assistant Professor, George Mason University
+1-703-993-9546

MASC Group: http://masc.cs.gmu.edu
Homepage: http://cs.gmu.edu/~jmlien