Lab Members

Short Biosketch

Video: Shoichet, channeling William F. Buckley, offers a vigorous defense of docking and high-throughput screening for the graduate student retreat (interviewed by Emily Crawford, channeling Steven Colbert).

Podcast: Shoichet, in a public interview, tries desperately to sound less confused than he actually is.

 Recent reviews, book chapters, and papers:

  • Shoichet BK. No free energy lunch. Nat Biotechnol 25 (10), 1109-10 (2007). [Pubmed | DOI | Download PDF]
  • Shoichet BK. Screening in a spirit haunted world. Drug Discov Today 11 (13-14), 607-15 (2006). [Pubmed | DOI | Download PDF]
  • Shoichet BK. Interpreting Steep Dose-Response Curves in Early Inhibitor Discovery. J Med Chem 49 (25), 7274-7277 (2006). [Pubmed | DOI | Download PDF]
  • Shoichet BK. Virtual Screening of Chemical Libraries (Review). Nature 432, 40-43 (2004). [Pubmed | DOI | PDF]
  • JJ Irwin & BK Shoichet.  Docking Screens for Novel Ligands Conferring New Biology. J. Med. Chem. 59, 4103-4120 (2016). [Pubmed | DOI | Download PDF]
  • BL Roth, JJ Irwin, BK Shoichet, Discovery of new GPCR ligands to illuminate new biology.  Nature Chemical Biology 13, 1143-1151 (2017). [Pubmed | DOI | Download PDF]

Alina Arzamassky (Tokmakova), Biophysics
Graduate Student

I use novel physical, computational, and chemical approaches to improve the scoring function in molecular docking. I design, implement and validate the scoring function of molecular docking by adding corrections to the calculation of van der Waals forces and entropic effect. The new scoring function in molecular docking will help to predict the binding affinity between the protein and ligand. In turn, this will help to identify novel small molecules that bind to a protein target of interest and therefore are useful starting points for drug discovery.


Elissa Fink, Biophysics
Graduate Student

My work focuses on using large-scale docking to discover ligands with designed polypharmacology or selectivity. I am also interested in leveraging the power of large-scale docking to identify novel analgesics for non-opioid targets.


Isabella Glenn,
Research Technician

My research focuses on both screening and uncovering new mechanistic insights on two common artifacts found in early drug discovery: colloidal aggregation and Phospholipidosis. I utilize biochemistry and cellular biology techniques to study these. Additionally, I have a background in protein crystallography and have a great interest in this as well.


Sijie Huang, Ph.D

Virtual screening has become somewhat a proven and well-appreciated computational method for hits identification and optimization. My research focuses on the application of ultra-large library docking techniques and the discovery of novel ligands against GPCRs involved in pain and other CNS disorders, as well as for COVID-19.


Anat Levit, Ph.D
DARPA Project Manager

Signal transduction is one of the most essential biological processes in all living organisms. G protein-coupled receptors (GPCRs) constitute the largest and most diverse family of cell surface receptors in the human genome, responsible for communicating messages between the cell's external and internal environments. A primary goal of my research is to integrate advancements in both our understanding of GPCR structure and in structure-based docking techniques, to realize the potential in targeting novel GPCR binding sites for drug discovery, as well as applying these techniques for exploring the functions of orphan GPCRs.

Publications :

  • Wang S, Che T, Levit A, Shoichet BK, Wacker D, Roth BL. Structure of the D2 dopamine receptor bound to the atypical antipsychotic drug risperidone. Nature 555 (7695), 269 (2018). [Pubmed | DOI | PDB 6CM4]
  • Wacker D, Wang S, McCorvy JD, Betz RM, Venkatakrishnan AJ, Levit A, Lansu K, Schools ZL, Che T, Nichols DE, Shoichet BK, Dror RO, Roth BL. Crystal Structure of an LSD-Bound Human Serotonin Receptor. Cell 168 (3), 377-389 (2017). [Pubmed | DOI | F1000 | Newsweek | Scientific American | Nature NEWS | PDB 5TVN]
  • Wang S, Wacker W, Levit A, Che T, Betz RM, McCorvy JD, Venkatakrishnan AJ, Huang XP, Dror RO, Shoichet BK, Roth BL. D4 dopamine receptor high-resolution structures enable the discovery of selective agonists. Science 358 (6361), 381-386 (2017). [DOI | UCSF News | PDB 5WIU | PDB 5WIV]
  • Manglik A, Lin H, Aryal DK, McCorvy JD, Dengler D, Corder G, Levit A, Kling RC, Bernat V, Hübner H, Huang XP, Sassano MF, Giguère PM, Löber S, Da Duan, Scherrer G, Kobilka BK, Gmeiner P, Roth BL, Shoichet BK. Structure-based discovery of opioid analgesics with reduced side effects. Nature 537, 185-190 (2016). [Pubmed | DOI | BioCentury | Download PDF]

Fangyu Liu, PhD

My project uses computational based molecular docking, an approach widely used for drug discovery. My interest has two foci: first, I am testing the impact of new, multi-billion compound libraries that the lab has introduced to the field, to discover new drug candidates by using a model system, and I am applying those new libraries to, in particular, discover new drug leads for a GPCR, which is involved in several genetic and metabolic diseases, and for which new drug leads are much wanted. In the future, I hope to expand my knowledge on pharmaceutical and medicinal chemistry and combine my background in structural biology and biochemistry to discover new chemical probes for mechanistic studies on membrane proteins.


Jiankun Lyu, Ph.D

Purchasable chemical space is growing rapidly. We are docking these ever increasing databases. I am exploring what happens to docking when we go to larger and larger databases. I am also working on developing analysis tools for the large-scale docking.

Publications :

  • Weiss, DR, Karpiak J, Huang XP, Sassano MF, Lyu J, Roth BL, Shoichet BK. Selectivity Challenges in Docking Screens for GPCR Targets and Anti-Targets. J Med Chem , (2018). [Pubmed | DOI]
  • Lyu J, Wang S, Balius TE, Singh I, Levit A, Moroz YS, O'Meara MJ, Che T, Algaa E, Tolmachova K, Tolmachev AA, Shoichet BK, Roth BL, Irwin JJ. Ultra-large library docking for discovering new chemotypes. Nature. 2019 Feb; 566(7743):224-229. [Pubmed | DOI]

Olivier Mailhot, Ph.D

GPCR dynamics play a central role in their activation mechanism. I am investigating fast computational methods to predict the function of novel ligands based on how they perturb the dynamics of active and inactive GPCR states. I am also working on heuristics to help in prioritizing subsets of the make-on-demand libraries as they keep on growing exponentially.


Joe O'Connell,
Lab Manager

Joe worked with Bob Stroud, Ph.D. at UCSF for over 20 years purifying and crystallizing membrane proteins. He is the lab manager for the Shoichet lab.

Publications :

  • Janet Finer-Moore, Nadine Czudnochowski, Joseph D.O'Connell III, Amy Liya Wang, Robert M.Stroud. Crystal Structure of the Human tRNA m1A58 Methyltransferase–tRNA3Lys Complex: Refolding of Substrate tRNA Allows Access to the Methylation Target. Journal of Molecular Biology. JMB, 2015
  • Brian C. Monk, Thomas M. Tomasiak, Mikhail V. Keniya, Franziska U. Huschmann, Joel D. A. Tyndall, Joseph D. O’Connell III, Richard D. Cannon, Jeffrey G. McDonald, Andrew Rodriguez, Janet S. Finer-Moore, and Robert M. Stroud. Architecture of a single membrane spanning cytochrome P450 suggests constraints that orient the catalytic domain relative to a bilayer. PNAS, 2014
  • John Edward Paka,1, Elisabeth Ngonlong Ekendéb,1, Efrem G. Kiflea, Joseph Daniel O’Connell III, Fabien De Angelisb, Meseret B. Tessemaa, Kheiro-Mouna Derfoufib, Yaneth Robles-Colmenaresa, Rebecca A. Robbinsa, Erik Goormaghtighb, Guy Vandenbusscheb, Robert M. Stroud. Structures of intermediate transport states of ZneA, a Zn(II)/proton antiporter. PNAS, 2013

Shiming Peng, Ph.D

My research focuses on novel ligand discovery for orphan and therapeutic GPCRs. Using large-scale docking, a library of hundreds-of-millions of make-on-demand molecules are docked against crystal structures and homology models of target receptors. Top-ranking molecules are tested experimentally. Active molecules are optimized using structure-based drug design methods.


Moira Michelle Rachman, Ph.D

My research interests include the development and application of computational drug design methods with an emphasis on structure-based and fragment-based strategies. Currently, I am involved in projects that aim to discover novel ligands for the SARS-CoV-2 macrodomain, as well as, the cannabinoid receptor, CB2.


Matthew Smith,
Graduate Student

Using MD-sampled energies in Flexible Receptor DOCK to improve drug discovery for T4 lysozyme and SARS-CoV-2 NSP3 Mac1, with applications to selectivity.


Tia Tummino, PSPG
Graduate Student

My work focuses on using large-scale molecular docking coupled with chemoinformatic methods to identify novel modulators of non-opioid pain signaling. I am particularly interested in the translation of in silico docking hits to in vitro and in vivo models, with an emphasis on understanding the pharmacodynamic effects of novel ligands at different levels of complexity. I use my graduate training in pharmaceutical sciences and molecular interactions as well as my undergraduate training in neuroscience to understand these complex systems.

Publications :

  • Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, O'Meara MJ, Guo JZ, Swaney DL, Tummino TA, Hüttenhain R, Kaake RM, Richards AL, Tutuncuoglu B, Foussard H, Batra J, Haas K, Modak M, Kim M, Haas P, Polacco BJ, Braberg H, Fabius JM, Eckhardt M, Soucheray M, Bennett MJ, Cakir M, McGregor MJ, Li Q, Naing ZZC, Zhou Y, Peng S, Kirby IT, Melnyk JE, Chorba JS, Lou K, Dai SA, Shen W, Shi Y, Zhang Z, Barrio-Hernandez I, Memon D, Hernandez-Armenta C, Mathy CJP, Perica T, Pilla KB, Ganesan SJ, Saltzberg DJ, Ramachandran R, Liu X, Rosenthal SB, Calviello L, Venkataramanan S, Lin Y, Wankowicz SA, Bohn M, Trenker R, Young JM, Cavero D, Hiatt J, Roth T, Rathore U, Subramanian A, Noack J, Hubert M, Roesch F, Vallet T, Meyer B, White KM, Miorin L, Agard D, Emerman M, Ruggero D, García-Sastre A, Jura N, von Zastrow M, Taunton J, Schwartz O, Vignuzzi M, d'Enfert C, Mukherjee S, Jacobson M, Malik HS, Fujimori DG, Ideker T, Craik CS, Floor S, Fraser JS, Gross J, Sali A, Kortemme T, Beltrao P, Shokat K, Shoichet BK, Krogan NJ. A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing. bioRxiv. 2020 Mar 22. [PubMed | DOI]

Seth Vigneron,
Graduate Student

The rapid growth of purchasable chemical space has been dominated by compounds formed via a handful of reactions, leaving many scaffolds with proven biological relevancy out of virtual databases. My work focuses on using advancements in organic synthesis to diversify synthetically tractable virtual libraries. I am also interested in how these underexplored chemotypes can be used as tools to improve ligand discovery and understand complex biological systems. My undergraduate experience in organic chemistry and graduate training in the UCSF Chemistry and Chemical Biology program inform my work.


Chase Webb, PSPG
Graduate Student

I am a joint graduate student in the Shoichet and Manglik Labs in the Pharmaceutical Sciences and Pharmacogenomics PhD program at UCSF. My background is in synthetic organic chemistry and natural product chemoenzymatic synthesis. I received my bachelor of science from Saint Mary's College of Califonia, and subsequently participated in the NIH PREP at Case Western Reserve University before matriculating at UCSF. I am interested in the pharmacology and structural biology of GPCR-mediated nociception. My work involves structure based design of novel analgesics targeting G-protein coupled receptors. 


Alex D. White, Ph.D

I am currently investigating the mechanistic basis of drug-induced phospholipidosis and its role as a confound in drug repurposing screens. I also have an interest in GPCR signal transduction mechanisms.

Publications :

  • Alex D. White, Lisa J. Clark, Shi Liu, Saifei Lei, Karina A. Peña, Frederic G. Jean-Alphonse, Zhiqiang Cheng, Chia-Ling Tu, Nicholas Szeto, James Krieger, Thomas J. Gardella, Ivet Bahar, Samuel H. Gellman, Wenhang Chang, and Jean-Pierre Vilardaga.  Spatial bias in cAMP generation determines biological responses to PTH type 1 receptor.  Sci. Signal. (2021).
  • Alex D. White, Frederic G. Jean-Alphonse, Shi Liu, Gabriele M. Konig, Asuka Inoue, Samuel H. Gellman, Evi Kostenis, and Jean-Pierre Vilardaga.  Gq/11-dependent regulation of endosomal cAMP generation by PTH class B GPCR.  Proc. Natl. Acad. Sci. USA (2020).
  • Alex D. White, Fei Fang, Frédéric G. Jean-Alphonse, Lisa J. Clark, Hyun-Jung An, Hongda Liu, Yang Zhao, Shelley L.Reynolds, Sihoon Lee, Kunhong Xiao, Ieva Sutkeviciute, and Jean-Pierre Vilardaga.  Ca2+ allostery in PTH-receptor signaling.  Proc. Natl. Acad. Sci. USA (2019).

Yujin Wu, Ph.D

My research focuses on developing a benchmarking system for evaluating free energy calculation methods in lead compound optimization, applying implicit solvent models in hit picking. I also work with Elissa Fink on using large-scale docking to discover ligands with designed polypharmacology or selectivity.