Narasinga Rao, Ph.D.
Molecular Drug Discovery Consultant
Adjunct Professor
Department of Chemistry & Biochemistry
UNC Greensboro
Greensboro, NC 27402
Title: Biomolecular structure-activity studies by NMR and computational methods
Abstract: Elucidation of three-dimensional structure and conformations of
biomolecules is a critical first step to understanding their biological activity. This
presentation will involve the application of NMR and computational methods for
exploring conformations of three different classes of bioactive molecules. The
first study relates to the determination of the 3D-structure of the anti-freeze
glycoprotein (AFGP), a biological antifreeze, found in certain species of Antarctic
fish. This protein is responsible for preventing the fish from freezing at ocean
temperatures below the freezing point of fish serum. The proposed model, a lefthanded three-fold helix, has been the generally accepted model for the lowmolecular fraction AFGP-8. The second topic deals with the identification and
design of a molecular mimetic of a natural carbohydrate receptor (SLe x) involved
in the adhesion of leukocytes to vascular endothelial cells. This analog, a
triterpene glycoside, was the first ever mimetic to be designed for a natural
carbohydrate epitope. Further, this work led to the design of other novel SLe x
mimetics and, to the introduction of the term “glycomimetic” into scientific lingo.
The third topic relates to a drug design application. In this study a structurebased design strategy was employed to improve the biological activity of a Gprotein coupled receptor kinase2 inhibitor.
Biographical sketch: Dr. Narasinga Rao is a biophysical chemist specialized in
the application of computational chemistry for drug discovery research. He has
eighteen years of biopharmaceutical industry experience and over 20 years of
post-Ph.D. research experience. Most recently, he was Senior Computational
Chemist at SCYNEXIS, where he was responsible for the application of
computational and informatics strategies for lead generation and optimization. He
also developed several computational tools to aid discovery work, including the
design and development of a knowledge-based expert system for kinase inhibitor
design and, implementation of a novel virtual screening process for identifying of
new chemical leads. In his earlier position at Glycomed Inc., he established the
computational chemistry and high field NMR facilities, managed the company’s
Biophysical Laboratory, and served as a member of the Research Management
Committee. Prior to joining SCYNEXIS, he worked at Chiron Corporation, where
he was the lead computational chemist on several of its discovery programs. He
also served as a liaison for structural chemistry between Chiron and its
collaborative partners, and supervised the collaboration between Chiron and
UCSF for the shared 600 MHz NMR instrument. Currently, he has been involved
in the activities of the Triad Drug discovery Discussion Group (TDDG), of which
he is a cofounder at UNC Greensboro. Dr. Rao is also a participating member of
the International Consortium on Antivirals (ICAV, Canada), a non-profit
organization engaged in the development of antivirals against pandemic and
emerging viral diseases.
Dr. Rao got his Ph.D. in Molecular Biophysics from Indian Institute of Science,
India and, did his post-doctoral work at Illinois Institute of Technology, Chicago.
Following a brief appointment as a research faculty member in the Dept. of
Biology at The Johns Hopkins University, he moved to industry to pursue his
interests in drug discovery research. Dr. Rao’s computational work has spanned
all three major classes of biological molecules - proteins carbohydrates and
nucleotides. He has used rational drug design strategies for a variety of protein
target classes that include kinases, proteases, MMP’s, cell-adhesion molecules
among others. Dr. Rao’s molecular design work on selectin inhibitors led him to
design the first ever mimetic of a natural carbohydrate ligand and introduce the
term “glycomimetics” into scientific lingo. Dr. Rao has 15 patents and has
authored 30 publications in peer-reviewed journals. He has given invited talks or
poster presentations at over 50 national/international scientific meetings.