An overarching interest is to bring chemical reagents to biology, using a combination of computational simulation and experiment. Using a protein-centric approach, we search for new ligands that complement protein structures. Using a ligand-centric approach, we try to find new targets for known drugs. A particular focus is the discovery of reagents to modulate G-Protein Coupled Receptors. Two crazy goals for the next five years are predicting one ligand for every accessible protein target, and for every drug predicting one new target to which it binds.
A Few Recent Papers:
- Chen Y, Shoichet BK. Molecular docking and ligand specificity in fragment-based inhibitor discovery. Nature Chemical Biology 5 (5), 358-364 (2009). [Pubmed | DOI | News and Views | Download PDF]
- 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]
- 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]
- Coan KE, Shoichet BK. Stoichiometry and physical chemistry of promiscuous aggregate-based inhibitors. J Am Chem Soc 130 (29), 9606-12 (2008). [Pubmed | DOI | Download PDF]
- Hermann JC, Marti-Arbona R, Fedorov AA, Fedorov E, Almo SC, Shoichet BK, Raushel FM. Structure-based activity prediction for an enzyme of unknown function. Nature 448 (7155), 775-9 (2007). [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]
We thank and OpenEye Scientific Software for software, BD Biosciences for a solubility scanner, Sunset Molecular for the Wombat database and John Overington/EBI for early access to StarLight.
We are grateful to the NIH National Institute of General Medical Sciences for financial support.