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Research & Reviews: Journal of Material Sciences | ISSN: 2321-6212 | Volulme 6
November 07-08, 2018 | Atlanta, USA
Materials Science and Engineering
15
th
International Conference and Exhibition on
Applied Crystallography
3
rd
International Conference on
&
The impact of crystallization conditions protein constructs and space groups on structure based drug
design
Orly Dym
Structural Proteomics Unit, Israel
T
he 3D structure of apo proteins and proteins with inhibitors provide the basis for structure-based drug design studies
and is also utilized in docking procedures to search for more potent drug. Specific examples for drug design of Acetyl
Cholinesterase (AChE) and Phosphotriesterase (PTE) using X-ray crystallography will be presented. Comparative analysis
between the computational docking drug design approach and the AChE crystal structures reviled that the position of the
ligands within the active-site gorge of the enzyme is influenced by the crystallization conditions. Spectroscopic evidence and
thermal stability results supported such a difference in ligand positioning. These results have implications for structure-based
drug design using docking procedures. We also analyzed nineteen crystal structures of the apo and several phosphonate (OP)
analogs bound to few highly evolved PTE variants. In addition to providing insights into the binding modes of OPs into the
active site of the different PTE variants, the data reveal the importance of tags used for protein expression, the ‘choice of the
appropriate’ crystallization conditions, the protein constructs and the space groups and their implications for structure-based
drug design.
Biography
Orly Dym completed her PhD in 1994 from the Weizmann Institute of Science, Israel under the supervision of Prof Joel Sussman and postdoctoral studies from
the University of California Los Angeles, under the supervision of Prof David Eisenberg. Since 2003 she is the Crystallographer at the Structural Proteomics Unit
(SPU), Weizmann Institute of Science, Israel. For the last 15 years she has been a member of the SPU where she lead the unit of protein crystallography which
include protein crystallization, elucidating the three-dimensional (3D) structure of proteins. She had determined the 3D structure of 350 proteins and protein
complexes, some related to human disease and others including engineered non-natural enzymes and non-natural protein complexes. Some has contributed to
the development of drugs, while one has directly benefited enzyme replacement therapy for a human disease. In addition, she has carried out detailed structural
analysis on many of these structures, which has greatly aided the understanding the correlation between 3D structure, function, selectivity and stability. She has
published more than 50 papers in reputed journals, 10 of which as first author.
orly.dym@weizmann.ac.ilOrly Dym, Res. Rev. J Mat. Sci. 2018, Volume 6
DOI: 10.4172/2321-6212-C8-035