Short biosketchvideo: 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]
Sarah Boyce
CCB Graduate studentI'm working with new model binding sites in cytochrome c peroxidase to investigate and improve the DOCK scoring function, specifically with an interest in receptor desolvation.
|  |
Publications: - Graves AP, Shivakumar DM, Boyce SE, Jacobson MP, Case DA, Shoichet BK. Rescoring docking hit lists for model cavity sites: predictions and experimental testing. J Mol Biol 377 (3), 914-34 (2008). [Pubmed | DOI | Download PDF]
- Brenk R, Vetter SW, Boyce SE, Goodin DB, Shoichet BK. Probing molecular docking in a charged model binding site. J Mol Biol 357 (5), 1449-70 (2006). [Pubmed | DOI | Download PDF]
Jens Carlsson, Ph. D.
PostdocProjects:
- Development of new docking methodology.
- Docking to model binding cavities.
- Identifying ligands of GPCRs using molecular docking.
|  |
Allison Doak
I have taken over the World of Small Molecule Aggregation from the amazing Dr. Kristin Coan. Main focus: can/do small molecules form colloidal particles in biologically relevant environments?
(Un-related) Publication:
Galli LM, Knight SR, Barnes TL, Doak AK, Kadzik RS, Burrus LW. Identification and characterization of subpopulations of Pax3 and Pax7 expressing cells in devloping chick somites and limb buds. Dev Dyn 237 (7), 1862-74 (2008).
|  |
Oliv Eidam, Ph. D.
PostdocI use docking, modeling and crystallography to find new cancer therapeutics and to fight bacterial resistance against penicillin-like antibiotics. My work is in collaborations with the NIH Chemical Genomics Center (NCGC), the Structural Genomics Consortium (SGC) in Oxford and dedicated synthetic chemists from the University of Modena in Italy.
I am also interested into fragment-based drug discovery.
Publications (from PhD)
|  |
Rafaela Salgado Ferreira
CCB Graduate Student (joint with James McKerrow Lab)I am interested in structure-based drug design, specially focusing on neglected diseases. My thesis work focuses on the cysteine protease cruzain, from Trypanosoma cruzi, the causative agent for Chagas' disease.
I have been on working on interdisciplinary projects involving virtual screening, medicinal chemistry, HTS and structural biology. My role is these projects consists in performing both virtual screening and follow up experiments. mainly in enzymology and crystallography.
|  |
Publications: - Teotico DG, Babaoglu K, Rocklin GJ, Ferreira RS, Giannetti AM, Shoichet BK. Docking for fragment inhibitors of AmpC beta-lactamase. PNAS 106 (18), 7455-60 (2009). [Pubmed | DOI | Download PDF]
- Kolb P, Ferreira RS, Irwin JJ, Shoichet BK. Docking and chemoinformatic screens for new ligands and targets.. Current opinion in biotechnology 20 (4), 429-36 (2009). [Pubmed | DOI | Download PDF]
John J. Irwin, Ph. D.
Adjunct Assistant ProfessorMy goal is to make virtual screening more useful for specialists and more accessible for everyone. Our first released product to address these goals is the ZINC database of commerically available compounds for virtual screening. For more information, please see my webpage.
|  |
Publications: - Kolb P, Rosenbaum DM, Irwin JJ, Fung JJ, Kobilka BK, Shoichet BK. Structure-based discovery of beta2-adrenergic receptor ligands. PNAS 106 (16), 6843-6848 (2009). [Pubmed | DOI | Download PDF]
- Irwin JJ, Shoichet BK, Mysinger MM, Huang N, Colizzi F, Wassam P, Cao Y. Automated docking screens: a feasibility study.. Journal of medicinal chemistry 52 (18), 5712-20 (2009). [Pubmed | DOI | Download PDF]
- Kolb P, Ferreira RS, Irwin JJ, Shoichet BK. Docking and chemoinformatic screens for new ligands and targets.. Current opinion in biotechnology 20 (4), 429-36 (2009). [Pubmed | DOI | Download PDF]
- Hert J, Keiser MJ, Irwin JJ, Oprea TI, Shoichet BK. Quantifying the Relationships among Drug Classes. J Chem Inf Model 48 (4), 755-765 (2008). [Pubmed | DOI | Download PDF]
- Babaoglu K, Simeonov A, Irwin JJ, Nelson ME, Feng B, Thomas CJ, Cancian L, Costi MP, Maltby DA, Jadhav A, Inglese J, Austin CP, Shoichet BK. Comprehensive mechanistic analysis of hits from high-throughput and docking screens against beta-lactamase. J Med Chem 51 (8), 2502-11 (2008). [Pubmed | DOI | Download PDF]
- Keiser MJ, Roth BL, Armbruster BN, Ernsberger P, Irwin JJ, Shoichet BK. Relating protein pharmacology by ligand chemistry. Nat Biotech 25 (2), 197-206 (2007). [Pubmed | DOI | Download PDF]
- Huang N, Kalyanaraman C, Irwin JJ, Jacobson MP. Physics-based scoring of protein-ligand complexes: enrichment of known inhibitors in large-scale virtual screening. J Chem Inf Model 46 (1), 243-53 (2006). [Pubmed | DOI]
- Huang N, Shoichet BK, Irwin JJ. Benchmarking sets for molecular docking. J Med Chem 49 (23), 6789-801 (2006). [Pubmed | DOI | Download PDF]
- Hermann JC, Ghanem E, Li Y, Raushel FM, Irwin JJ, Shoichet BK. Predicting Substrates by Docking High-Energy Intermediates to Enzyme Structures. J Am Chem Soc 128 (49), 15882-891 (2006). [Pubmed | DOI | Download PDF]
- Irwin JJ, Shoichet BK. ZINC - A Free Database of Commercially Available Compounds for Virtual Screening. J Chem Inf Model 45 (1), 177-82 (2005). [Pubmed | DOI | Supporting Info | Download PDF]
- Brenk R, Irwin JJ, Shoichet BK. Here be dragons: docking and screening in an uncharted region of chemical space. J Biomol Screen 10 (7), 667-74 (2005). [Pubmed | DOI | Download PDF]
- Irwin JJ, Raushel FM, Shoichet BK. Virtual screening against metalloenzymes for inhibitors and substrates. Biochemistry 44 (37), 12316-28 (2005). [Pubmed | DOI | Download PDF]
- Atreya CE, Johnson EF, Irwin JJ, Dow A, Massimine KM, Coppens I, Stempliuk V, Beverley S, Joiner KA, Shoichet BK, Anderson KS. A molecular docking strategy identifies eosin B as a non-active Site Inhibitor of protozoal bifunctional thymidylate synthase-dihydrofolate reductase. J Biol Chem 278 (16), 14092-100 (2003). [Pubmed | DOI | Faculty of 1000 | Download PDF]
- Shoichet BK, McGovern SL, Wei B, Irwin JJ. Lead discovery using molecular docking (Review). Current Opinion in Chemical Biology 6, 439-46 (2002). [Pubmed | DOI | Download PDF]
Michael Keiser
BMI Graduate StudentI'm developing chemoinformatics techniques to relate proteins based on the statistical similarity of their ligands. I apply this method to questions of polypharmacology, functional relatedness, and virtual screening.
|  |
Publications: - Hert J, Keiser MJ, Irwin JJ, Oprea TI, Shoichet BK. Quantifying the Relationships among Drug Classes. J Chem Inf Model 48 (4), 755-765 (2008). [Pubmed | DOI | Download PDF]
- Keiser MJ, Roth BL, Armbruster BN, Ernsberger P, Irwin JJ, Shoichet BK. Relating protein pharmacology by ligand chemistry. Nat Biotech 25 (2), 197-206 (2007). [Pubmed | DOI | Download PDF]
Peter Kolb, Ph. D.
PostdocDiscovering enzyme functions through the identification of substrates using DOCK. For more information, please see my webpage.
| |
Publications: - Xiang D, Kolb P, Fedorov A, Meier M, Fedorov E, Nguyen T, Sterner R, Almo S, Shoichet B, Raushel F. Functional Annotation and Three-Dimensional Structure of Dr0930 from Deinococcus radiodurans, a Close Relative of Phosphotriesterase in the Amidohydrolase Superfamily. Biochemistry 48 (10), 2237-2247 (2009). [Pubmed | DOI]
- Kolb P, Rosenbaum DM, Irwin JJ, Fung JJ, Kobilka BK, Shoichet BK. Structure-based discovery of beta2-adrenergic receptor ligands. PNAS 106 (16), 6843-6848 (2009). [Pubmed | DOI | Download PDF]
- Kolb P, Ferreira RS, Irwin JJ, Shoichet BK. Docking and chemoinformatic screens for new ligands and targets.. Current opinion in biotechnology 20 (4), 429-36 (2009). [Pubmed | DOI | Download PDF]
Publications:
Matthew Merski, Ph. D.
PostdocI am studying the ligand binding capabilities of the cavities in the model proteins T4 phage enzymes and yeast cytochrome C peroxidase. By mutating residues within these cavities and determining the binding affinities of ligands I hope to tease out the energetic terms associated with complex formation.
| |
Michael Mysinger
PSPG Graduate StudentMy project focuses on improving DOCK's predictions of ligand binding affinities, including research on how to better access our predictive performance and how to improve our scoring models. In order to improve ligand binding predictions, we first need to accurately measure our current docking performance. To this end, I have focused on automated DUD-style decoy generation, in order to automatically produce property-matched decoys given a set a active ligands by using the ZINC database. I then in turn use these improved benchmarking databases to study improvements to DOCK 3.5's desolvation model. In our newest ligand desolvation model, we use Generalized-Born theory to compute the percentage desolvation of each ligand atom, which is then used to scale its "true" atomic desolvation energy.
| |
Publications: - Irwin JJ, Shoichet BK, Mysinger MM, Huang N, Colizzi F, Wassam P, Cao Y. Automated docking screens: a feasibility study.. Journal of medicinal chemistry 52 (18), 5712-20 (2009). [Pubmed | DOI | Download PDF]
Gabriel Rocklin
Biophysics Graduate Student (Joint with Ken Dill's lab)I am working on applying molecular dynamics simulations and alchemical free energy methods to the problem of predicting absolute binding free energies in the model binding sites. I hope to increase the speed and reliability of these calculations, and also to use this highest level of computational theory available to learn lessons about ligand binding that will applicable to docking.
|  |
Publications: - Teotico DG, Babaoglu K, Rocklin GJ, Ferreira RS, Giannetti AM, Shoichet BK. Docking for fragment inhibitors of AmpC beta-lactamase. PNAS 106 (18), 7455-60 (2009). [Pubmed | DOI | Download PDF]
Veena L. Thomas
PSPG Graduate studentActivity and Stability Consequences of Evolution of Inhibitor-Resistant Beta-Lactamase Mutants.
| |
Publications: - Thomas VL, Golemi-Kotra D, Kim C, Vakulenko SB, Mobashery S, Shoichet BK. Structural consequences of the inhibitor-resistant Ser130Gly substitution in TEM beta-lactamase. Biochemistry 44 (
26), 9330-9338 (2005). [Pubmed | DOI | Download PDF]
Dahlia Weiss, Ph. D.
PostdocMovement is crucial to protein-ligand interactions, yet experimentally determined crystallographic structures of proteins can give us only a static snapshot. I aim to develop methods for virtual screen that will allow protein target flexibility. I use multi-conformational docking screens to discover a broad range of novel chemotypes and binding conformations relevant to the activation of the beta-2-adrenergic receptor.
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
|  |
|
