|
Bethesda Marriott, Bethesda, MD
May 8-10, 2002
Sponsored by: National Institute on Drug Abuse
Symposium Chair: Dr. Rao S. Rapaka, NIDA
Co-Chairs: Dr. Paul Hillery, NIDA; Dr.Karen Skinner, NIDA
Meeting Summary
This symposium was organized to update the progress in this area and
to explore the new areas of research to be encouraged in future and to
promote research related to drug abuse and, more specifically to
enhance NIDA's programs in drug design. The first talk of the
symposium was given by Dr. James Colliver, NIDA and he presented an
overview of the epidemiological patterns of some selected drugs of
abuse. The second talk was from Dr. Jerome Karle, Nobel Laureate,
Naval Research laboratories, and he was the keynote speaker. He gave
an overview on quantum crystallography and all the recent developments
in the area. Rest of the symposium consisted of four sessions, and
the sessions were on, structure determination, receptors, transporters
and mechanisms, structural genomics and proteomics and, ligands and
therapeutics.
In the first session, Dr. Wlodawer reported on the determination of
the crystal structure of a pepstatin-insensitive carboxyl proteinase
from pseudomonas. Dr. Deschamps summarized some of the results from
hundreds of ligands studied resulting from the NIDA-NRL interagency
agreement. Dr. Choe described the structural parameters for calcium
channels and Dr. Brennan spoke on multidrug binding proteins. Dr.
Subramaniam gave a nice summary on the advances in the imaging of
molecular assemblies with electron cryo-microscopy and this talk was
later followed by Dr. Ramakrishnan on the molecular mechanical
devices. Dr. Zuiderweg gave a presentation on the utilization of
recent NMR techniques to study protein interactions and this talk was
followed by Dr. Amzel's talk on the structure and mechanism of the
mitochondrial ATP-synthase. Dr. Glaser gave a review on the techniques
for crystallization of membrane proteins from connected-bilayer gels.
In the second session, Dr. Mark Mayer discussed the molecular
mechanisms of desensitization for glutamate receptor ion channels.
Dr. Kobilka's talk was on the ligand-specific conformational changes
of the beta-2 adrenergic receptor, Dr. Javitch's talk was on
oligomerization of the human dopamine receptor and the molecular
mechanisms involved and Dr. Rudnick's presentation was on the
serotonin transporter. Dr. Harel Weinstein gave a nice overview on
signaling in membrane proteins and computational models of several
transmembrane helices, role of proline in the formation of
proline-kinks, and also presented data on the utilization of
computational models to study molecular dynamics. Dr. Reggio
described, from her computational studies, the structural features of
the cannabinoid ligands for binding at the CB-1 receptor as inverse
agonists. Dr. David Farrens gave a comparative study of the
structural and structure-dependent functional properties of the
cannabinoid and rhodopsin receptors. Dr. Mierke spoke on
receptor-protien interactions using NMR and Dr. Patel gave an overview
of FRET and demonstrated the applicability of this technique for the
analysis of the ligand-receptor stoichiometry and aggregation states
for three receptors systems. He demonstrated that this technique
could be applied to live cells. Dr. Goodman demonstrated how the
structural studies on the ligand-receptor system could help in ligand
design.
In the third session, Dr. Patterson gave a summary of how proteomics
techniques can be helpful in drug discovery, Dr. Cravatt gave an
update on chemical approaches for functional proteomics and Dr. Gavin
MaBeath gave an overview on protein microarrays and their applications
to functional genomics and high-throughput screening. Dr. Stevens
presented his talk on the application of high throughput techniques
for drug design and Dr. Skolnick spoke on prediction of protein
structure and function on a genomic scale. Dr. Neubig gave a talk on
how RGS protein can serve as new targets for drug design for CNS
therapeutics.
The last session was devoted to ligand design. Dr. Cascio spoke on
the how the altered bilayer composition can effect the glycine
receptor. Dr. Mosberg presented an impressive amount of data on
ligand-receptor interactions and ligand design in the opioid area.
Dr. Makriyannis described the design of cannabinoid ligands based in
the structural biology models including the two new potent ligands,
Mahanadamide and Paramandamide. Dr. Deber gave talk on polar
mutations in membrane proteins and how these mutations may lead to
genetic disease. Dr. Victor Hruby gave a overview of plasmon
waveguide resonance spectroscopy and how this method can be used to
differentiate agonist, antagonist and inverse agonist interaction
without resorting to expense and laborious methods to synthesize
labeled ligands.
These sessions were followed by several discussion sessions. Several
recommendations have emerged from this symposium. There was
an universal recognition among the participants that the time is ripe
for undertaking a large number of structural biology studies and
understanding the structure of ion channels, receptors, enzymes,
proteins, lipids, and ligands is crucial. There was an agreement on
developing new methodologies and application of presently available
methods to the problems at hand. It was also suggested that bright
chemists and biologists should be attracted to conduct research in
this area by awarding "beginners grants" who could later really
develop into established researchers concentrating in the CNS
disorders and more specially in drug abuse research.
|
|
|