Dahlia Weiss



Nurix, Inc.

1700 Owens Street

San Francisco, CA



dahlia.weiss at gmail.com



Key words: Drug design; Computational chemistry; Structural biology



CURRENT Research Interests


Senior Scientist, Nurix Inc, San Francisco, USA

E2 conjugating enzymes and E3 ligases control protein stability and protein fate through the Ubiquitin Proteasome System (UPS). Small molecule enhancers and inhibitors of E2 and E3 enzymes provide an innovative path to regulate key actors in cell fate through regulation of the UPS, and may be particularly relevant in oncology and inflammatory disease. I am applying computer aided drug design to target this challenging class of Protein-Protein Interfaces, including drugablilty analysis, hit identification, virtual fragment based drug design and lead optimization.






Structural Biology / Chemistry


Department of Chemistry, Stanford University, USA


Advisor: Professor M Levitt, Computational Structural Biology lab


Joint B.S. Magna cum laude

Chemistry and Biology


Department of Chemistry and Department of Biology, Tel Aviv University, Israel



      DR Weiss, J Karpiak, XP Huang, MF Sassanno, J Lyu, BL Roth, BK Shoichet; Selectivity Challenges in Docking Screens for GPCR Targets and Antitargets Journal of medicinal chemistry 61 (15), 6830-6845 (2018)

      M Korczynska, MJ Clark, C Valant, J Xu, E Von Moo, S Albold, DR Weiss,...,RK Sunahara ; Structure-based discovery of selective positive allosteric modulators of antagonists for the M2 muscarinic acetylcholine receptor Proceedings of the National Academy of Sciences 115 (10) E2419-E2428 (2018)

      DR Weiss, A Bortolato, B Tehan, JS Mason; GPCR-Bench: A Benchmarking Set and Practitioners’ Guide for G Protein-Coupled Receptor Docking Journal of chemical information and modeling 56 (4),642-651 (2016)

      A Bortolato, F Deflorian, DR Weiss, JS Mason; Decoding the Role of Water Dynamics in Ligand–Protein Unbinding: CRF1R as a Test Case Journal of chemical information and modeling 55 (9), 1857-1866 (2015)

      Bennet, KA; Doré, AS, Christopher, JA; Weiss, DR; Marshall, FH; Structures of mGluRs shed light on the challenges of drug development of allosteric modulators Current Opinion in Pharmacology 20:1–7 (2015)

      Silva, DA; Weiss, DR; Avila, FD; Da, LT; Levitt, M; Wang, D; Huang, X;  Millisecond dynamics of RNA polymerase II translocation at atomic resolution Proceedings of the National Academy of Sciences 111 (21) : 7665-7670 (2014)

      Weiss, DR; Koehl, P;  Morphing Methods to Visualize Coarse-Grained Protein Dynamics Protein Dynamics : 271-282 (2014)

      Coleman, RG; Sterling, T; Weiss, DR;  SAMPL4 & DOCK3. 7: lessons for automated docking procedures Journal of Computer-Aided Molecular Design : 41883 (2014)

      Weiss, DR*; Ahn, SK*; Sassano, MF; Kleist, A; Zhu, X; Strachan, R; Roth, BL; Lefkowitz, RJ; Shoichet, BK;  Conformation Guides Molecular Efficacy in Docking Screens of Activated β-2 Adrenergic G Protein Coupled Receptor ACS chemical biology (8) : 1018-1026 (2013)    *equal contributors

      Kruse, AC*; Weiss, DR*; Rossi, M; Hu, J; Hu, K; Eitel, K; Gmeiner, P; Wess, J; Kobilka, BK; Shoichet, BK;  Muscarinic Receptors as Model Targets and Antitargets for Structure-Based Ligand Discovery Molecular pharmacology (84) : 528-540 (2013)      *equal contributors

      Mason, JS*; Bortolato, A*; Weiss, DR*; Deflorian, F; Tehan, B; Marshall, FH;  High end GPCR design: crafted ligand design and druggability analysis using protein structure, lipophilic hotspots and explicit water networks In Silico Pharmacology (1) : 23 (2013)      *equal contributors

      Mysinger, MM*; Weiss, DR*; Ziarek, JJ*; Gravel, S; Doak, AK; Karpiak, J; Heveker, N; Shoichet, BK; Volkman, BF;  Structure-based ligand discovery for the protein–protein interface of chemokine receptor CXCR4 Proceedings of the National Academy of Sciences (109) : 5517-5522 (2012)    *equal contributors

      Bray, JK; Weiss, DR; Levitt, M;  Optimized Torsion-Angle Normal Modes Reproduce Conformational Changes More Accurately Than Cartesian Modes Biophysical journal (101) : 2966 (2011)

   Huang, X; Wang, D; Weiss, DR; Bushnell, DA; Kornberg, RD; Levitt, M;  RNA polymerase II trigger loop residues stabilize and position the incoming nucleotide triphosphate in transcription Proceedings of the National Academy of Sciences (107) : 15745-15750 (2010)

   Weiss, DR; Levitt, M;   Can morphing methods predict intermediate structures? Journal of molecular biology (385) : 665-674 (2009)

   Weiss, DR; Raschke, TM; Levitt, M;  How hydrophobic buckminsterfullerene affects surrounding water structure The Journal of Physical Chemistry B (112) : 2981-2990 (2008)

All manuscripts in preparation and in press can be viewed as PDF on request


Awards and Honors


NIH NRSA for Individual Postdoctoral Fellows, F32 GM093580-01, UCSF
Following a successful grant application, I was awarded NIH funding for 3 years.



SimBios, NIH Center for Biomedical Computation, Full fellowship, Stanford
SimBios is an NIH funded center, awarding up to 3 full doctoral fellowships each year.



Program in Mathematics and Molecular Biology, Full fellowship, Stanford
The PMMB is a national research and training consortium funded by a Burroughs Wellcome Fund Interfaces grant (now discontinued), granting ten doctoral awards each year.



Wise Scholarship for Masters Studies, Full fellowship, Tel Aviv University


Magna cum laude, B.S. Studies, Chemistry and Biology





PAST Research Interests


Senior Scientist, Computer Aided Drug Design, Heptares Therapeutics Limited, UK

G-protein coupled receptors (GPCRs), are the largest superfamily of proteins in the human body, and are the targets of >30% of all marketed drugs. At Heptares Therapeutics, I applied computer aided drug design to challenging GPCR targets as part of the drug discovery team. I led the development of new computational methods for structure-based design, including the use of water structure in docking and lead optimization, MD simulation and prediction of drug binding kinetics.


Post-doctoral research, Shoichet lab, Department of Pharmaceutical Chemistry, University of California, San Francisco, USA

I applied virtual screening and GPCR homology modeling for the discovery of new chemical matter for these therapeutically important targets. I was interested in the rational design of selectivity for receptor subtypes and ligand efficacy.


Visiting scholar, INRIA, French National Institute for Research in Computer Science and Control,  France

Geometries of waters at protein-protein interfaces in the dynamic setting

We used computational geometry to study the interaction and dynamics of water in the protein-protein interface.


Ph.D. Studies, Levitt Lab, 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. The interpolation is now used as a starting point for long-time-scale simulation 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, with important implications for nanomaterials.


M.S. Studies, Department of Biochemistry, Tel Aviv University, Israel

The Anti-Codon Nuclease active site

We used multiple sequence alignment and secondary structure predictions to study a t-RNA nuclease with anti-HIV potential. Predicted mutations were experimentally shown to alter cleavage patterns, with possible therapeutic applications.


B.S. Studies, Department of Biotechnology, Tel Aviv University, Israel

Kinetics of self-assembly in amyloidal fibrils: Biophysical studies

We used biophysical measurements (CD and ELISA) to characterize the kinetics of self-assembly in amyloid fibrils.



Head Teaching Assistant


Computational Structural Biology,   Stanford University


Teaching Assistant and Laboratory Instructor


General Chemistry; Organic Chemistry Stanford University

General Chemistry, Tel Aviv University



President, Israeli Student Organization


I served as president of the Israeli Student Organization at Stanford for two years. I created and managed a budget of over $8000, oversaw a mailing list and website, and organized events for over 150 members.


IT Administrator, Biox Super Computing Cluster


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.


Non-Commissioned Officer, Israeli Defense Forces


I served in the Israeli army in a diplomatic capacity. I corresponded regularly 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.


Invited Talks And workshops

American Chemical Society National Meeting, San Francisco, USA “GPCR drug-binding kinetics: Insights from explicit water network modeling”

August 2014

Spring Symposium KNCV Medicinal Chemistry, Utrecht, Netherlands “Water molecules in drug target structures”

March 2014

Royal Society of Chemistry and Biochemical Society, London, UK “Tools and Strategies to Find Chemical Probes for Your Protein - The Role of Computer-Aided Drug Discovery”

November 2013

American Chemical Society National Meeting, New Orleans, USA “G-protein coupled receptors in virtual screening: Functional fidelity and selectivity”
Session chair, “Protein-Ligand Interactions: Insights, New Tools and Applications in Drug Design”

April 2013

Skyline College, USA, “Using computers to design drugs”

March 2012

Uppsala University, Sweden, “Multiresolution Molecular Simulation Workshop”

June 2011

Duke University, USA “Dockblaster and SEA tutorial”

Sept 2011

University of Science and Technology, Hong Kong, “Virtual screening of B2 Adrenergic Receptor”

April 2010

San Jose State University, USA, “Hydrophobic hydration”

Feb 2010

University of New Orleans, USA, “Non-linear morphing”

Jan 2009

Stockholm University, Sweden, “Can morphing predict intermediate structures?”

April 2008

INRIA, France, “Interactions of water with small hydrophobic solutes”

March 2008

Tel Aviv University, Israel, “The Myosin II Motion Pathway”

Dec 2005