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]

Enkhjargal Algaa
Scientific Programmer

I studied Computer Science with specialization in Database Management Systems at University of Jena, Germany. I'm happy to join BKS lab team as Scientific Programmer.

Enkhjargal

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 | Download PDF]

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:

  • Lee H, Fischer M, Shoichet BK, and Liu SY. Hydrogen Bonding of 1,2-Azaborines in the Binding Cavity of T4 Lysozyme Mutants: Structures and Thermodynamics. J. Am. Chem. Soc. , ASAP (2016). [DOI]
  • 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 | Download PDF]
  • Fischer M, Shoichet BK, Fraser JS. One Crystal, Two Temperatures: Cryocooling Penalties Alter Ligand Binding to Transient Protein Sites. Chembiochem. 16 (11), 1560-4 (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 | Download PDF]
  • 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"> | Download PDF]

Inbar Fish

Publications:

  • Lacroix C, Fish I, Torosyan H, Parathaman P, Irwin JJ, Shoichet BK, Angers S. Identification of Novel Smoothened Ligands Using Structure-Based Docking.. PLoS One 11 (8), e0160365 (2016). [Pubmed | DOI]
  • 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 | Download PDF]
  • 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"> | Download PDF]

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:

  • Korczynska M, Le DD, Younger N, Gregori-Puigjané E, Tumber A, Krojer T, Velupillai S, Gileadi C, Nowak RP, Iwasa E, Pollock SB, Torres IO, Oppermann U, Shoichet BK, Fujimori DG. Docking and Linking of Fragments To Discover Jumonji Histone Demethylase Inhibitors. J. Med. Chem. 59 (4), 1580-1598 (2016). [Pubmed | DOI | Practical Fragments | UCSF Pharmacy - Recent Research]
  • 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 | Download PDF]
  • 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. Functional annotation and structural characterization of a novel lactonase hydrolyzing D-xylono-1,4-lactone-5-phosphate and L-arabino-1,4-lactone-5-phosphate. Biochemistry 53 (28), 4727-2738 (2014). [Pubmed | DOI | Download PDF]
  • 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

Publications:

  • 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]

Matthew O'Meara, Ph. D.
Postdoc



Matthew

Publications:

  • O'Meara MJ, Ballouz S, Shoichet BK, Gillis J. Ligand Similarity Complements Sequence, Physical Interaction, and Co-Expression for Gene Function Prediction. PLoS ONE 11 (7), e0160098 (2016). [DOI]

Josh Pottel, Ph. D.
Postdoc

I graduated from McGill with my Ph. D in chemistry focusing on computational modeling of bio- and organo-catalysis. My work now involves overcoming fundamental challenges in charting the role of metabolic signalling in medicinal chemistry. I am improving the Similarity Ensemble Approach (SEA) software to capture and discriminate metabolite-like molecules which are often more reactive, have more degrees of freedom, and have greater symmetry than stable, rigid and functionally diverse drug-like molecules. The improved target prediction will illuminate new signalling processes and enable the design of effective polypharmacology to support The Metabolic Code hypothesis.

Josh

Publications:

  • Irwin JJ, Pottel J, Zou L, Wen H, Zuk S, Zhang X, Sterling T, Shoichet BK, Lionberger R, Giacomini KM. A Molecular Basis for Innovation in Drug Excipients. Clin Pharmacol Ther. (epub), (2016). [Pubmed | DOI]

Kate A. Stafford, Ph. D.
Postdoctoral Fellow

I work on modeling and docking to discover ligands for the so-called "orphan" GPCRs, or receptors for which endogenous ligands are not known. I also work on methods development for optimizing homology models to identify known ligands.

Kate

Reed Stein
PSPG Graduate Student

My work aims to incorporate receptor desolvation, the displacement of solvent from the binding site upon ligand binding, into the DOCK scoring function, a term which is currently neglected. This new term relies on continuum electrostatics, a quick method that represents the solvent as a homogeneous high dielectric medium. I will experimentally test ligands predicted from this new scoring function using binding assays and X-ray crystallography in a model cavity.

Reed

Hayarpi Torosyan
Research Associate

Hayarpi

Publications:

  • McLaughlin CK, Duan D, Ganesh AN, Torosyan H, Shoichet BK, Shoichet MS. Stable Colloidal Drug Aggregates Catch and Release Active Enzymes. ACS Chem. Biol. 11 (4), 992-1000 (2016). [Pubmed | DOI]
  • Lacroix C, Fish I, Torosyan H, Parathaman P, Irwin JJ, Shoichet BK, Angers S. Identification of Novel Smoothened Ligands Using Structure-Based Docking.. PLoS One 11 (8), e0160365 (2016). [Pubmed | DOI]
  • Irwin JJ, Duan D, Torosyan H, Doak AK, Ziebart KT, Sterling T, Tumanian G, Shoichet BK. An Aggregation Advisor for Ligand Discovery. J Med Chem. 58 (17), 7076-87 (2015). [Pubmed | DOI | In The Pipeline | Practical Fragments]

Xiaobo Wan, Ph. D.
Postdoctoral Fellow

I am developing efficient computational docking pipelines for covalent inhibitor design. Now I have a special interest in designing lysine covalent probes by combine a variety of computational and experimental methods. My ultimate goal is to design covalent drugs for traditionally undruggable targets.

Xiaobo

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