UCSF

Shoichet Laboratory

Lab members


Brian K. Shoichet, Ph. D.
Professor

Brian
Short biosketch

video: Shoichet, channeling William F. Buckley, offers a vigorous defense of docking and high-throughput screening for the graduate student retreat (interviewedby 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. 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]

Trent Balius, Ph. D.
Postdoc

I am working on performing large-scale docking and improving automated docking procedures. The objective is to perform proteomic-scale docking and analyse the results in cool ways to learn about protein relationships from a ligand-centered perspective. My goal is to obtain a faculty position at a research university were I plan to continue DOCK development and perform research focused on drug discovery and improving therapeutics. For more information about me visit my webpage: http://docking.org/~tbalius/

Trent

Publications:

  • Merski M, Fischer M, Balius TE, Eidam O, Shoichet BK. Homologous ligands accommodated by discrete conformations of a buried cavity. PNAS 112 (16), 5039-5044 (2015). [Pubmed | DOI]

Sarah Barelier, Ph. D.
Postdoc

I am interested in fragment-based approaches applied to drug design and substrate discovery:

  • Fragment-based screening against AmpC Beta-Lactamase: how to expand our exploration of chemical space using fragment molecules?
  • Analyzing the potential of fragment molecules as tools for enzyme function prediction: the Amidohydrolase Superfamily as a case study. These two projects involve fragment docking, enzymatic assays and X-ray crystallography.

Publications from PhD



Sarah

Publications:

  • Barelier S, Cummings JA, Rauwerdink AM, Hitchcock DS, Farelli JD, Almo SC, Raushel FM, Allen KN, Shoichet BK. Substrate deconstruction and the nonadditivity of enzyme recognition. J Am Chem Soc. 136 (20), 7374-82 (2014). [Pubmed | DOI | Chem & Eng NEWS | Practical Fragments Blog]
  • Barelier S, Eidam O, Fish I, Hollander J, Figaroa F, Nachane R, Irwin JJ, Shoichet BK, Siegal G. Increasing chemical space coverage by combining empirical and computational fragment screens. ACS Chem Biol 9 (7), 1528-35 (2014). [Pubmed | DOI | Practical Fragments Blog]
  • Barelier S, Boyce SE, Fish I, Fischer M, Goodin DB, Shoichet BK. Roles for ordered and bulk solvent in ligand recognition and docking in two related cavities.. PLoS One 8 (7), e69153 (2013). [Pubmed | DOI | Download PDF]
  • Eidam O, Romagnoli C, Dalmasso G, Barelier S, Caselli E, Bonnet R, Shoichet BK, Prati F.. Fragment-guided design of subnanomolar β-lactamase inhibitors active in vivo.. Proc Natl Acad Sci U S A 109 (43), 17448-53 (2012). [Pubmed | DOI | Download PDF]

Allison Doak

I study small molecule colloidal aggregation and its effects on compound screening and drug development, using in vitro methods, such as dynamic light scattering and enzyme kinetics assays, in biochemical buffers, cell culture media, and simulated gastric fluids. Our current research areas focus on these questions:

  • Can and do small molecules form collodial particles in biologically relevant environments, and can this phenomenon affect drug absorption in vivo?
  • If so, can we predict in vivo behavior based on in vitro collodial characteristics, and therefore, can we improve drug delivery using these techniques?


Allison

Publications:

  • Duan D, Doak AK, Nedyalkova L, Shoichet BK. Colloidal aggregation and the in vitro activity of traditional chinese medicines. Chemical Biology 10 (4), 978-988 (2015). [Pubmed | DOI]
  • Owen SC, Doak AK, Ganesh AN, Nedyalkova L, McLaughlin CK, Shoichet BK, Shoichet MS. Colloidal drug formulations can explain "bell-shaped" concentration-response curves. ACS Chem Biol. 9 (3), 777-84 (2014). [Pubmed | DOI]
  • Benod C, Carlsson J, Uthayaruban R, Hwang P, Irwin JJ, Doak AK, Shoichet BK, Sablin EP, Fletterick RJ. Structure-based Discovery of Antagonists of Nuclear Receptor LRH-1. J Biol Chem 288 (27), 19830-44 (2013). [Pubmed | DOI]
  • Sassano MF, Doak AK, Roth BL, Shoichet BK. Colloidal aggregation causes inhibition of G protein-coupled receptors. J Med Chem 56 (6), 2406-14 (2013). [Pubmed | DOI | Download PDF]
  • 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. Proc Natl Acad Sci 109 (14), 5517-22 (2012). [Pubmed | DOI | Download PDF]
  • Rogers KE, Keränen H, Durrant JD, Ratnam J, Doak A, Arkin MR, McCammon JA. Novel cruzain inhibitors for the treatment of Chagas' disease.. Chem Biol Drug Des. 80 (3), 398-405 (2012). [Pubmed | DOI]
  • Doak AK, Wille H, Prusiner SB, Shoichet BK. Colloid Formation by Drugs in Simulated Intestinal Fluid. J. Med. Chem. 53 (10), 4259-4265 (2010). [Pubmed | DOI | Download PDF]
  • Galli LM, Knight SR, Barnes TL, Doak AK, Kadzik RS, Burrus LW. Identification and characterization of subpopulations of Pax3 and Pax7 expressing cells in developing chick somites and limb buds.. Dev Dyn 237 (7), 1862-74 (2008). [Pubmed | DOI]

Da Duan, Ph. D.
Postdoc

The formation of soluble colloids(aggregates) by small organic molecules including well-known drugs is a phenomenon discovered in the Shoichet lab more than a decade ago. Although some physical characteristics of these colloids have been investigated, the biophysical basis of this phenomenon is largely unknown. A primary goal of my research is to understand the mechanism of colloid formation at the atomic level. A second area of my researches focuses upon the idea of whether there is a relationship between drug colloids and their pharmacokinetics in vivo. A third area of interest is the utilization of colloidal drug formulations to enhance specificity and efficacy of drug delivery.

Da

Publications:

  • Duan D, Doak AK, Nedyalkova L, Shoichet BK. Colloidal aggregation and the in vitro activity of traditional chinese medicines. Chemical Biology 10 (4), 978-988 (2015). [Pubmed | DOI]

Marcus Fischer, Ph. D.
Postdoc

I'm working with model systems to develop and experimentally test computational methods for ligand discovery. For those simplified, engineered cavities the cycle between prediction and testing is rapid and informative. It is one of the few systems where failure is illuminating, even sought. I have a general interest in understanding phenomena underlying protein-ligand interactions which I study using a variety of complementary methods.
Other Publications



Marcus

Publications:

  • Merski M, Fischer M, Balius TE, Eidam O, Shoichet BK. Homologous ligands accommodated by discrete conformations of a buried cavity. PNAS 112 (16), 5039-5044 (2015). [Pubmed | DOI]
  • Fischer M, Coleman RG, Fraser JS, Shoichet BK. Incorporation of protein flexibility and conformational energy penalties in docking screens to improve ligand discovery. Nature Chemistry 6 (7), 575-583 (2014). [Pubmed | DOI]
  • Barelier S, Boyce SE, Fish I, Fischer M, Goodin DB, Shoichet BK. Roles for ordered and bulk solvent in ligand recognition and docking in two related cavities.. PLoS One 8 (7), e69153 (2013). [Pubmed | DOI | Download PDF]
  • Rocklin GJ, Boyce SE, Fischer M, Fish I, Mobley DL, Shoichet BK, Dill KA. Blind prediction of charged ligand binding affinities in a model binding site.. J Mol Biol 425 (22), 4569-83 (2013). [Pubmed | DOI | Access the recommendation on F1000Prime">]

Inbar Fish

Publications:

  • Barelier S, Eidam O, Fish I, Hollander J, Figaroa F, Nachane R, Irwin JJ, Shoichet BK, Siegal G. Increasing chemical space coverage by combining empirical and computational fragment screens. ACS Chem Biol 9 (7), 1528-35 (2014). [Pubmed | DOI | Practical Fragments Blog]
  • Barelier S, Boyce SE, Fish I, Fischer M, Goodin DB, Shoichet BK. Roles for ordered and bulk solvent in ligand recognition and docking in two related cavities.. PLoS One 8 (7), e69153 (2013). [Pubmed | DOI | Download PDF]
  • Rocklin GJ, Boyce SE, Fischer M, Fish I, Mobley DL, Shoichet BK, Dill KA. Blind prediction of charged ligand binding affinities in a model binding site.. J Mol Biol 425 (22), 4569-83 (2013). [Pubmed | DOI | Access the recommendation on F1000Prime">]

Magdalena Korczynska, Ph. D.
Postdoc

I received my Doctoral dissertation from McGill University, in the field of X-ray crystallographic studies of antibiotic resistance enzymes. Now, as a Postdoctoral Fellow, I am involved with the Enzyme Function Initiative (EFI) project (http://enzymefunction.org/). This is a multi institutional, collaborative endeavor that has been set up to identify an efficient work flow to reliably identify in vitro enzymatic activity and in vivo metabolic function from sequence. My specific contribution to the EFI project is to computationally predict the function of enzymes based on the complementary of metabolic substrates to the three dimensional protein structure.

Magdalena

Publications:

  • London N, Farelli JD, Brown SD, Liu C, Huang H, Korczynska M, Al-Obaidi NF, Babbitt PC, Almo SC, Allen KN, Shoichet BK. Covalent docking predicts substrates for haloalkanoate dehalogenase superfamily phosphatases. Biochemistry 54 (2), 528-537 (2015). [Pubmed | DOI]
  • Korczynska M, Xiang DF, Zhang Z, Xu C, Narindoshvili T, Kamat SS, Williams HJ, Chang SS, Kolb P, Hillerich B, Sauder JM, Burley SK, Almo SC, Swaminathan S, Shoichet BK, Raushel FM. Homologous ligands accommodated by discrete conformations of a buried cavity. Biochemistry 53 (28), 4727-2738 (2014). [Pubmed | DOI]
  • Ornelas A, Korczynska M, Ragumani S, Kumaran D, Narindoshvili T, Shoichet BK, Swaminathan S, Raushel FM. Functional annotation and three-dimensional structure of an incorrectly annotated dihydroorotase from cog3964 in the amidohydrolase superfamily. Biochemistry 52 (1), 228-38 (2013). [Pubmed | DOI | Download PDF]

Anat Levit, Ph. D.
Postdoc

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.

Anat

Matthew O'Meara, Ph. D.
Postdoc



Matthew

Hayarpi Torosyan
Research Associate


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