Dahlia Weiss
University of California, San Francisco Mission Bay Campus, Byers Hall 1700 4th Street, 5^th Floor, Room 501 San Francisco, CA 94158-2330	Office: (415) 514-4253 dahlia.weiss at gmail.com http://csb.stanford.edu/dahlia
Key words: Docking; Molecular dynamics; Computational chemistry; Structural biology

Education
Ph.D.	Structural Biology / Chemistry	2003-2009
Department of Chemistry, Stanford University, USA
Pre-Doctoral Research with Professor Michael Levitt, Computational Structural Biology lab
M.S. Studies	Biochemistry	2001-2003
Department of Biochemistry, Tel Aviv University, Israel
Pre-Masters Research with Professor Gabriel Kaufmann
Joint B.S. Magna cum laude	Chemistry and Biology	1998-2001
Department of Chemistry and Department of Biology, Tel Aviv University, Israel
Undergraduate Research with Doctor Ehud Gazit
Research Interests
Post-doctoral research, Shoichet lab, University of California, San Francisco, USA
G-protein coupled receptors (GPCRs), are the largest superfamily of proteins in the human body, are ubiquitous players in normal and diseased cell signal transduction, and represent >30% of all marketed therapeutics. We are investigating the applicability of structure based drug design, and the use of GPCR homology modeling in particular, for the discovery of new chemical matter for these therapeutically important targets. Virtual screening of the agonist bound β2AR structure GPCRs display a complex spectrum of signaling behaviors, likely reflecting multiple functionally relevant conformations of the receptor. The recently solved active β2 Adrenergic Receptor (β2AR) structure revealed surprisingly subtle changes in the ligand binding site upon agonist binding. In contrast to the inactive β2AR structure, which predicted only inverse-agonists, with virtual screening the agonist-bound structure predicted 6 agonists, some with potencies equaling Isoproterenol, and only 2 weak antagonists. Of the 6 agonists found, 2 are completely novel partial agonists that activate the β2AR through previously unknown functional groups. Modeling β-arrestin vs. G-protein mediated signaling conformations In addition to signaling through the G-protein, GPCRs can also stimulate β-arrestin mediated signaling, often leading to positive clinical outcomes. We are currently engaged in modeling the β-arrestin biased β2AR conformation. Compounds will be selected from a virtual screen of the modeled structure and experimentally tested for bias. Modeling active GPCR for virtual screening More generally, we asked whether the active β2AR structure could act as modeling template, predicting new active GPCR structures for virtual screening? We have modeled active D2 and D1 Dopamine Receptor structures for virtual screening. Virtual screening and ligand selectivity in aminergic GPCR Weight gain, a common and serious side effect of most antipsychotic drugs, is thought to be mediated by unwanted interaction with histamine receptors. Using the recently solved H1 Histamine Receptor crystal structure, as well as a modeled 5HT2A Serotonin Receptor structure and modeled D2 Dopamine Receptor structure in virtual screening, we are searching for new molecules that can selectively modulate the behavior of dopamine and serotonin receptors, without affecting the histamine receptors. Virtual screening of the Protein-Protein Interface of Chemokine Receptor CXCR4 Chemokine receptor CXCR4 is directly implicated in HIV infection and more than 20 different types of cancer. Protein-protein interfaces (PPI) such as that presented by CXCR4 are notoriously difficult to modulate with “drug-like” small molecules, and so despite intense interest, few potent inhibitors have been discovered for this target. We conducted a virtual screen of the CXCR4 crystal structure and discovered 4 novel and potent inhibitors, all with favorable physical properties, and all biologically active in cells. Prior to release of the crystal structure, we virtually screened a CXCR4 homology model, prosecuting one of the first blind and prospective comparisons of a GPCR homology model in predictive virtual screening to a crystal structure.
Visiting scholar, INRIA, French National Institute for Research in Computer Science and Control, France
Geometries of waters and residues at protein-protein interfaces in the dynamic setting
We used computational geometry methods (specifically Voronoi polyhedra) to study the interaction of water molecules and protein in the protein-protein interaction interface in a dynamic setting.
Ph.D. Studies, Department of Chemistry, Stanford University, USA
Coarse graining of protein dynamics
Protein dynamics important to biological function often happen on a time scale that is unattainable through detailed simulation methods such as molecular dynamics (MD). We developed a novel interpolation method to study transitions between known crystal structures that does not extrapolate motion linearly and can therefore move around high energy barriers. We propesed a novel test set of high-fidelity protein structures with at least three crystallographic on-pathway intermediate structures from the Protein Databank (PDB) to asses with an objective criteria the biological significance of coarse-grained dynamics methods.
Simulated behavior of nanoscale hydrophobic solutes in water
Using MD simulation, we studied details of the water structure surrounding a single molecule of Buckminsterfullerene (C60). We showed ordering of water in both the first and second hydration shell, and an increase of hydrogen bonding within shells. This has important implications for nanoscale solutes.
M.S. Studies, Department of Biochemistry, Tel Aviv University, Israel
The Anti-Codon Nuclease active site
Multiple sequence alignment and secondary structure predictions are to suggest single point mutations in the anti-codon nuclease active site, which we then characterized in vitro and in vivo. We showed an altered restriction activity with a number of the mutations we tested.
B.S. Studies, Department of Biotechnology, Tel Aviv University, Israel
Kinetics of self-assembly in amyloidal fibrils: Biophysical studies
We used biophysical measurements such as CD and ELISA to characterize the kinetics of self-assembly in amyloid fibrils.
Leadership Skills and Experience
President, Israeli Student Organization		2005-2007
I served on the steering committee of the Israeli Student Organization at Stanford for one year and was subsequently elected president for two years. I created and managed a budget of over $8000, and organized events for over 150 members, and oversaw three popular mailing lists and a website.
IT Administrator, Biox Super Computing Cluster		2004-2005
I supported a parallel computer cluster of 300 dual processors (600 CPUs), and 1TB network attached storage. As part of the IT admin team, I added and maintained hundreds of user accounts, answered user queries, weighed in on policy decisions and maintained FAQs.
Teaching Assistant and Laboratory Instructor		2001-2006
Computational Structural Biology, Autumn 2005, Autumn/Spring 2006, I was a teaching assistant for large undergraduate level chemistry classes, with duties including grading assignments and test papers and leading discussion sessions. I was involved in developing an online graduate- and professional-level course concentrating on current topics in Bioinformatics, and I was the head teaching assistant for that course for two years.
Non-Commissioned Officer, Israeli Defense Forces		1997-1999
I served in the Israeli army in a diplomatic capacity. I worked closely with the American Embassy in Tel Aviv as well as other embassies. I corresponded daily with high-level foreign dignitaries, organized meetings, and resolved problems in real time. As a NCO, I set priorities and tasks for subordinate soldiers, directed the archiving of classified information and supervised proper protocol with foreign agencies.
Awards and Honors
UCSF		2009-present
NIH NRSA for Individual Postdoctoral Fellows, F32 GM093580-01
Stanford University		2003-2009
Fellow, SimBios at the NIH Center for Biomedical Computation at Stanford
Fellow, Program in Mathematics and Molecular Biology
Tel Aviv University		2001-2003
Fellow, Wise Faculty of Life Sciences Scholarship for Masters Studies
Magna cum laude, B.S. Studies, Chemistry and Biology
Languages
Human English (Mother tongue), Hebrew (Native), French (Fluent) Machine C, C++, Fortran95, Perl, HTML, UNIX shell, AWK, MATLAB
Publications
Weiss DR, Raschke TM, Levitt M (2008), How Hydrophobic Buckminsterfullerene Affects Surrounding Water Structure, J Chem Phys B 112 (10) : 2981-90.   Weiss DR, Levitt M (2009), Can Morphing Methods Predict Intermediate Structures?, J Mol Biol 385 : 665-674 Huang X, Wang D, Weiss DR, Bushnell D, Kornberg RD, Levitt M (2010) RNA polymerase II trigger loop residues stabilize and position the incoming nucleotide triphosphate in transcription, Proc Natl Acad Sci 107 (36) : 15745-15750 Bray JK, Weiss DR, Levitt M (2011) Optimized Torsion-Angle Normal Modes Reproduce Conformational Changes More Accurately Than Cartesian Modes Biophys J 101 (12) : 2966-2969 Mysinger MM*, Weiss DR*, Ziarek J*, Gravel S, Doak AK, Karpiak J, Heveker H, Shoichet BK, Volkman BF (2012, accepted) Structure-Based Ligand Discovery for the Protein-Protein Interface of Chemokine Receptor CXCR4 Proc Natl Acad Sci *equal contributors
Invited Talks
Tel Aviv University, Israel, Bioinformatics Seminar “The Myosin II Motion Pathway”			Dec 2005
Stockholm University, Sweden, Center for Biomembrane Research Seminar “Can morphing predict intermediate structures?”			April 2008
University of New Orleans, USA, Protein Folding Group Seminar “Non-linear morphing”			Jan 2009
San Jose State University, USA, Chemistry Seminar “Geometric details of the interactions of water with small hydrophobic solutes”			Feb 2010
Hong Kong University of Science and Technology, Hong Kong, CCB Seminar “Virtual screening of the Beta-2 Adrenergic Receptor”			April 2010
Uppsala University, Sweden, Multiresolution Molecular Simulation Workshop “Prospecting on the Frontier” & “Dockblaster tutorial”			June 2011