Tanja Kortemme, PhD
Professor
Bioengineering
School of Pharmacy

Our research aims to invent approaches to engineer new molecules that operate as predicted in biological contexts, and to utilize prediction and engineering to address fundamental questions on the relationship of molecular mechanisms and systems-level function. To address the many current challenges in the field – from developing more predictive computational design methods to determining the requirements for function in cells – we combine concepts from computer science, physics, chemistry, mathematics, engineering and biology.

Our work spans three interrelated themes:

I. Develop computational methods for modeling & design of proteins, in the program Rosetta (www.rosettacommons.org).

Predicting and designing the structures of proteins with biologically useful accuracy has been a key challenge in computational structural biology and molecular engineering. We have made methodological advances that address one of the main bottlenecks: sampling the vast number of conformations accessible to proteins. We have utilized a method for moving through conformational space inspired by principles from robotics – a field with a rich history in efficient calculation of mechanically accessible states subject to constraints. We applied the same mathematics that can be used to direct the motions of a robot arm to compute the degrees of freedom of a polypeptide chain (Mandell et al., Nature Methods 2009). Our predictions generate hypotheses on protein conformations controlling biological processes – such as protein recognition, signal transduction, and enzyme active site gating – and are laying the foundation for our work reengineering and “reshaping” protein interfaces and active sites for new functions. From March-August 2020, we rapidly deployed our methods to engineer ACE2-based receptor traps that potently neutralize live SARS-CoV-2 virus in cell culture as therapeutic candidates for further development (Glasgow et al., PNAS 2020). Most recently, we developed an approach to engineer a vast universe of new proteins with tunable shapes (Pan et al., Science 2020).

II. Create new proteins and devices with more advanced functions by experimental engineering.

Designer molecules with new biological functions could have many exciting uses: protein therapeutics with minimal side effects; sensor/actuator devices that can report on cell biological processes in real time; robust signaling systems that can detect specific inputs and generate a precise response; protein machines that can be controlled by specific external inputs such as light or fueled by electron transfers. Over the past several years, we have engineered a range of proteins with new functions, including protein-protein interactions that are specific enough to control complex biological processes in mammalian cells (Kapp*, Liu* et al., PNAS, 2012). We have also engineered proteins whose functions can be switched by phosphorylation or light. One example is a study describing the control of precise shape transitions of a large protein assembly with optical inputs, where we successfully exchanged the ‘engine’ of a protein-based ATP-driven molecular machine to be powered by light (Hoersch et al., Nature Nanotechnology 2013). Most recently, we have focused on application of computational protein design to endow cells with the ability to sense and respond to new molecular signals and orchestrate desired biological responses, one of the most fundamental capabilities of living systems (Glasgow*, Huang*, Mandell* et al., Science 2019).

III. Dissect design principles of function in cells by combining prediction and engineering approaches.

The complexity of biological interaction networks makes it impossible at present to accurately predict the effects of perturbations to the network, such as expression changes or mutations, and, consequently, how to intervene effectively when networks are misregulated. To address this problem, we have become increasingly interested in approaches that quantify the complex cellular consequences of perturbations to biological networks together with their underlying mechanisms. In 2012, we published a study on engineered perturbations to a classic system for regulatory mechanisms of gene expression: the lac operon (Eames & Kortemme, Science 2012). A current experimental effort is directed towards determining the system-level functions of specific interactions in cells and organisms by systematically modulating protein interactions and protein abundance. In collaboration with Nevan Krogan’s laboratory at UCSF, we have made systematic mutational perturbations in a central GTPase molecular switch conserved in all eukaryotes (Perica, Mathy et al., bioRxiv 2021). By integrating functional genetic and proteomics approaches with biophysics, we find that distinct biological processes are differentially sensitive to the kinetics of switching, addressing the long-standing question of how a single molecular switch can differentially regulate different cellular functions. We hope that these principles of cellular control can guide cellular engineering, and ultimately lead to new and more precise ways to counteract misregulation in disease.

• Author Correction: Ligand-specific changes in conformational flexibility mediate long-range allostery in the lac repressor.
  Nature communications 2023 Glasgow A, Hobbs HT, Perry ZR, Wells ML, Marqusee S, Kortemme T
• Multi-input Drug-Controlled Switches of Mammalian Gene Expression Based on Engineered Nuclear Hormone Receptors.
  ACS synthetic biology 2023 Kretschmer S, Perry N, Zhang Y, Kortemme T
• Emerging maps of allosteric regulation in cellular networks.
  Current opinion in structural biology 2023 Mathy CJP, Kortemme T
• Ligand-specific changes in conformational flexibility mediate long-range allostery in the lac repressor.
  Nature communications 2023 Glasgow A, Hobbs HT, Perry ZR, Wells ML, Marqusee S, Kortemme T
• A complete allosteric map of a GTPase switch in its native cellular network.
  Cell systems 2023 Mathy CJP, Mishra P, Flynn JM, Perica T, Mavor D, Bolon DNA, Kortemme T
• Computational pipeline provides mechanistic understanding of Omicron variant of concern neutralizing engineered ACE2 receptor traps.
  Structure (London, England : 1993) 2023 Remesh SG, Merz GE, Brilot AF, Chio US, Rizo AN, Pospiech TH, Lui I, Laurie MT, Glasgow J, Le CQ, Zhang Y, Diwanji D, Hernandez E, Lopez J, Mehmood H, Pawar KI, Pourmal S, Smith AM, Zhou F, QCRG …
• Multi-input drug-controlled switches of mammalian gene expression based on engineered nuclear hormone receptors.
  bioRxiv : the preprint server for biology 2023 Kretschmer S, Perry N, Zhang Y, Kortemme T
• Computational pipeline provides mechanistic understanding of Omicron variant of concern neutralizing engineered ACE2 receptor traps.
  bioRxiv : the preprint server for biology 2022 Remesh SG, Merz GE, Brilot AF, Chio US, Rizo AN, Pospiech TH, Lui I, Laurie MT, Glasgow J, Le CQ, Zhang Y, Diwanji D, Hernandez E, Lopez J, Pawar KI, Pourmal S, Smith AM, Zhou F, QCRG Structural …
• Correction to "The Rosetta All-Atom Energy Function for Macromolecular Modeling and Design".
  Journal of chemical theory and computation 2022 Alford RF, Leaver-Fay A, Jeliazkov JR, O'Meara MJ, DiMaio FP, Park H, Shapovalov MV, Renfrew PD, Mulligan VK, Kappel K, Labonte JW, Pacella MS, Bonneau R, Bradley P, Dunbrack RL, Das R, Baker D, …
• Advances in the Computational Design of Small-Molecule-Controlled Protein-Based Circuits for Synthetic Biology.
  Proceedings of the IEEE. Institute of Electrical and Electronics Engineers 2022 Kretschmer S, Kortemme T
• Accurate positioning of functional residues with robotics-inspired computational protein design.
  Proceedings of the National Academy of Sciences of the United States of America 2022 Krivacic C, Kundert K, Pan X, Pache RA, Liu L, Conchúir SO, Jeliazkov JR, Gray JJ, Thompson MC, Fraser JS, Kortemme T
• Ensuring scientific reproducibility in bio-macromolecular modeling via extensive, automated benchmarks.
  Nature communications 2021 Koehler Leman J, Lyskov S, Lewis SM, Adolf-Bryfogle J, Alford RF, Barlow K, Ben-Aharon Z, Farrell D, Fell J, Hansen WA, Harmalkar A, Jeliazkov J, Kuenze G, Krys JD, Ljubetic A, Loshbaugh AL, Maguire J…
• De novo protein fold families expand the designable ligand binding site space.
  PLoS computational biology 2021 Pan X, Kortemme T
• Systems-level effects of allosteric perturbations to a model molecular switch.
  Nature 2021 Perica T, Mathy CJP, Xu J, Jang G?, Zhang Y, Kaake R, Ollikainen N, Braberg H, Swaney DL, Lambright DG, Kelly MJS, Krogan NJ, Kortemme T
• Design principles of protein switches.
  Current opinion in structural biology 2021 Alberstein RG, Guo AB, Kortemme T
• Reply to Liu et al.: Specific mutations matter in specificity and catalysis in ACE2.
  Proceedings of the National Academy of Sciences of the United States of America 2021 Glasgow J, Glasgow A, Kortemme T, Wells JA
• Recent advances in de novo protein design: Principles, methods, and applications.
  The Journal of biological chemistry 2021 Pan X, Kortemme T
• Engineered ACE2 receptor traps potently neutralize SARS-CoV-2.
  Proceedings of the National Academy of Sciences of the United States of America 2020 Glasgow A, Glasgow J, Limonta D, Solomon P, Lui I, Zhang Y, Nix MA, Rettko NJ, Zha S, Yamin R, Kao K, Rosenberg OS, Ravetch JV, Wiita AP, Leung KK, Lim SA, Zhou XX, Hobman TC, Kortemme T, Wells JA
• Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms.
  Science (New York, N.Y.) 2020 Gordon DE, Hiatt J, Bouhaddou M, Rezelj VV, Ulferts S, Braberg H, Jureka AS, Obernier K, Guo JZ, Batra J, Kaake RM, Weckstein AR, Owens TW, Gupta M, Pourmal S, Titus EW, Cakir M, Soucheray M, McGregor…
• New computational protein design methods for de novo small molecule binding sites.
  PLoS computational biology 2020 Lucas JE, Kortemme T
• Expanding the space of protein geometries by computational design of de novo fold families.
  Science (New York, N.Y.) 2020 Pan X, Thompson MC, Zhang Y, Liu L, Fraser JS, Kelly MJS, Kortemme T
• Altered expression of a quality control protease in E. coli reshapes the in vivo mutational landscape of a model enzyme.
  eLife 2020 Thompson S, Zhang Y, Ingle C, Reynolds KA, Kortemme T
• The Global Phosphorylation Landscape of SARS-CoV-2 Infection.
  Cell 2020 Bouhaddou M, Memon D, Meyer B, White KM, Rezelj VV, Correa Marrero M, Polacco BJ, Melnyk JE, Ulferts S, Kaake RM, Batra J, Richards AL, Stevenson E, Gordon DE, Rojc A, Obernier K, Fabius JM, Soucheray…
• Macromolecular modeling and design in Rosetta: recent methods and frameworks.
  Nature methods 2020 Leman JK, Weitzner BD, Lewis SM, Adolf-Bryfogle J, Alam N, Alford RF, Aprahamian M, Baker D, Barlow KA, Barth P, Basanta B, Bender BJ, Blacklock K, Bonet J, Boyken SE, Bradley P, Bystroff C, Conway P,…
• Better together: Elements of successful scientific software development in a distributed collaborative community.
  PLoS computational biology 2020 Koehler Leman J, Weitzner BD, Renfrew PD, Lewis SM, Moretti R, Watkins AM, Mulligan VK, Lyskov S, Adolf-Bryfogle J, Labonte JW, Krys J, RosettaCommons Consortium, Bystroff C, Schief W, Gront D, …
• A SARS-CoV-2 protein interaction map reveals targets for drug repurposing.
  Nature 2020 Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O'Meara MJ, Rezelj VV, Guo JZ, Swaney DL, Tummino TA, Hüttenhain R, Kaake RM, Richards AL, Tutuncuoglu B, Foussard H, Batra J, Haas K, …
• Computational design of a modular protein sense-response system.
  Science (New York, N.Y.) 2019 Glasgow AA, Huang YM, Mandell DJ, Thompson M, Ritterson R, Loshbaugh AL, Pellegrino J, Krivacic C, Pache RA, Barlow KA, Ollikainen N, Jeon D, Kelly MJS, Fraser JS, Kortemme T
• Comparison of Rosetta flexible-backbone computational protein design methods on binding interactions.
  Proteins 2019 Loshbaugh AL, Kortemme T
• Quantitative mapping of protein-peptide affinity landscapes using spectrally encoded beads.
  eLife 2019 Nguyen HQ, Roy J, Harink B, Damle NP, Latorraca NR, Baxter BC, Brower K, Longwell SA, Kortemme T, Thorn KS, Cyert MS, Fordyce PM
• Controlling CRISPR-Cas9 with ligand-activated and ligand-deactivated sgRNAs.
  Nature communications 2019 Kundert K, Lucas JE, Watters KE, Fellmann C, Ng AH, Heineike BM, Fitzsimmons CM, Oakes BL, Qu J, Prasad N, Rosenberg OS, Savage DF, El-Samad H, Doudna JA, Kortemme T
• Computational design of structured loops for new protein functions.
  Biological chemistry 2019 Kundert K, Kortemme T
• Extending chemical perturbations of the ubiquitin fitness landscape in a classroom setting reveals new constraints on sequence tolerance.
  Biology open 2018 Mavor D, Barlow KA, Asarnow D, Birman Y, Britain D, Chen W, Green EM, Kenner LR, Mensa B, Morinishi LS, Nelson CA, Poss EM, Suresh P, Tian R, Arhar T, Ary BE, Bauer DP, Bergman ID, Brunetti RM, Chio …
• Flex ddG: Rosetta Ensemble-Based Estimation of Changes in Protein-Protein Binding Affinity upon Mutation.
  The journal of physical chemistry. B 2018 Barlow KA, Ó Conchúir S, Thompson S, Suresh P, Lucas JE, Heinonen M, Kortemme T
• Engineering a light-activated caspase-3 for precise ablation of neurons in vivo.
  Proceedings of the National Academy of Sciences of the United States of America 2017 Smart AD, Pache RA, Thomsen ND, Kortemme T, Davis GW, Wells JA
• Deconstruction of the Ras switching cycle through saturation mutagenesis.
  eLife 2017 Bandaru P, Shah NH, Bhattacharyya M, Barton JP, Kondo Y, Cofsky JC, Gee CL, Chakraborty AK, Kortemme T, Ranganathan R, Kuriyan J
• The Rosetta All-Atom Energy Function for Macromolecular Modeling and Design.
  Journal of chemical theory and computation 2017 Alford RF, Leaver-Fay A, Jeliazkov JR, O'Meara MJ, DiMaio FP, Park H, Shapovalov MV, Renfrew PD, Mulligan VK, Kappel K, Labonte JW, Pacella MS, Bonneau R, Bradley P, Dunbrack RL, Das R, Baker D, …
• Determination of ubiquitin fitness landscapes under different chemical stresses in a classroom setting.
  eLife 2016 Mavor D, Barlow K, Thompson S, Barad BA, Bonny AR, Cario CL, Gaskins G, Liu Z, Deming L, Axen SD, Caceres E, Chen W, Cuesta A, Gate RE, Green EM, Hulce KR, Ji W, Kenner LR, Mensa B, Morinishi LS, Moss…
• A Model for the Molecular Mechanism of an Engineered Light-Driven Protein Machine.
  Structure (London, England : 1993) 2016 Hoersch D, Kortemme T
• Design of Light-Controlled Protein Conformations and Functions.
  Methods in molecular biology (Clifton, N.J.) 2016 Ritterson RS, Hoersch D, Barlow KA, Kortemme T
• Coupling Protein Side-Chain and Backbone Flexibility Improves the Re-design of Protein-Ligand Specificity.
  PLoS computational biology 2015 Ollikainen N, de Jong RM, Kortemme T
• A Web Resource for Standardized Benchmark Datasets, Metrics, and Rosetta Protocols for Macromolecular Modeling and Design.
  PloS one 2015 Ó Conchúir S, Barlow KA, Pache RA, Ollikainen N, Kundert K, O'Meara MJ, Smith CA, Kortemme T
• Combined covalent-electrostatic model of hydrogen bonding improves structure prediction with Rosetta.
  Journal of chemical theory and computation 2015 O'Meara MJ, Leaver-Fay A, Tyka MD, Stein A, Houlihan K, DiMaio F, Bradley P, Kortemme T, Baker D, Snoeyink J, Kuhlman B
• Quantification of the transferability of a designed protein specificity switch reveals extensive epistasis in molecular recognition.
  Proceedings of the National Academy of Sciences of the United States of America 2014 Melero C, Ollikainen N, Harwood I, Karpiak J, Kortemme T
• Editorial overview: Engineering and design: raising the bar through innovation and integration.
  Current opinion in structural biology 2014 Koide S, Kortemme T
• Reprogramming an ATP-driven protein machine into a light-gated nanocage.
  Nature nanotechnology 2013 Hoersch D, Roh SH, Chiu W, Kortemme T
• Computational protein design quantifies structural constraints on amino acid covariation.
  PLoS computational biology 2013 Ollikainen N, Kortemme T
• Amino-acid site variability among natural and designed proteins.
  PeerJ 2013 Jackson EL, Ollikainen N, Covert AW, Kortemme T, Wilke CO
• Design of a photoswitchable cadherin.
  Journal of the American Chemical Society 2013 Ritterson RS, Kuchenbecker KM, Michalik M, Kortemme T
• Serverification of molecular modeling applications: the Rosetta Online Server that Includes Everyone (ROSIE).
  PloS one 2013 Lyskov S, Chou FC, Conchúir SÓ, Der BS, Drew K, Kuroda D, Xu J, Weitzner BD, Renfrew PD, Sripakdeevong P, Borgo B, Havranek JJ, Kuhlman B, Kortemme T, Bonneau R, Gray JJ, Das R
• Improvements to robotics-inspired conformational sampling in rosetta.
  PloS one 2013 Stein A, Kortemme T
• Flexible backbone sampling methods to model and design protein alternative conformations.
  Methods in enzymology 2013 Ollikainen N, Smith CA, Fraser JS, Kortemme T
• Scientific benchmarks for guiding macromolecular energy function improvement.
  Methods in enzymology 2013 Leaver-Fay A, O'Meara MJ, Tyka M, Jacak R, Song Y, Kellogg EH, Thompson J, Davis IW, Pache RA, Lyskov S, Gray JJ, Kortemme T, Richardson JS, Havranek JJ, Snoeyink J, Baker D, Kuhlman B
• Design of a phosphorylatable PDZ domain with peptide-specific affinity changes.
  Structure (London, England : 1993) 2012 Smith CA, Shi CA, Chroust MK, Bliska TE, Kelly MJS, Jacobson MP, Kortemme T
• Prediction of mutational tolerance in HIV-1 protease and reverse transcriptase using flexible backbone protein design.
  PLoS computational biology 2012 Humphris-Narayanan E, Akiva E, Varela R, Ó Conchúir S, Kortemme T
• Cost-benefit tradeoffs in engineered lac operons.
  Science (New York, N.Y.) 2012 Eames M, Kortemme T
• Control of protein signaling using a computationally designed GTPase/GEF orthogonal pair.
  Proceedings of the National Academy of Sciences of the United States of America 2012 Kapp GT, Liu S, Stein A, Wong DT, Reményi A, Yeh BJ, Fraser JS, Taunton J, Lim WA, Kortemme T
• Global landscape of HIV-human protein complexes.
  Nature 2011 Jäger S, Cimermancic P, Gulbahce N, Johnson JR, McGovern KE, Clarke SC, Shales M, Mercenne G, Pache L, Li K, Hernandez H, Jang GM, Roth SL, Akiva E, Marlett J, Stephens M, D'Orso I, Fernandes J, Fahey…
• A mechanism for tunable autoinhibition in the structure of a human Ca2+/calmodulin- dependent kinase II holoenzyme.
  Cell 2011 Chao LH, Stratton MM, Lee IH, Rosenberg OS, Levitz J, Mandell DJ, Kortemme T, Groves JT, Schulman H, Kuriyan J
• Predicting the tolerated sequences for proteins and protein interfaces using RosettaBackrub flexible backbone design.
  PloS one 2011 Smith CA, Kortemme T
• Assessment of flexible backbone protein design methods for sequence library prediction in the therapeutic antibody Herceptin-HER2 interface.
  Protein science : a publication of the Protein Society 2011 Babor M, Mandell DJ, Kortemme T
• ROSETTA3: an object-oriented software suite for the simulation and design of macromolecules.
  Methods in enzymology 2011 Leaver-Fay A, Tyka M, Lewis SM, Lange OF, Thompson J, Jacak R, Kaufman K, Renfrew PD, Smith CA, Sheffler W, Davis IW, Cooper S, Treuille A, Mandell DJ, Richter F, Ban YE, Fleishman SJ, Corn JE, Kim DE…
• Construction of a genetic multiplexer to toggle between chemosensory pathways in Escherichia coli.
  Journal of molecular biology 2010 Moon TS, Clarke EJ, Groban ES, Tamsir A, Clark RM, Eames M, Kortemme T, Voigt CA
• SNX27 mediates PDZ-directed sorting from endosomes to the plasma membrane.
  The Journal of cell biology 2010 Lauffer BE, Melero C, Temkin P, Lei C, Hong W, Kortemme T, von Zastrow M
• Structure-based prediction of the peptide sequence space recognized by natural and synthetic PDZ domains.
  Journal of molecular biology 2010 Smith CA, Kortemme T
• RosettaBackrub--a web server for flexible backbone protein structure modeling and design.
  Nucleic acids research 2010 Lauck F, Smith CA, Friedland GF, Humphris EL, Kortemme T
• Designing ensembles in conformational and sequence space to characterize and engineer proteins.
  Current opinion in structural biology 2010 Friedland GD, Kortemme T
• Computer-aided design of functional protein interactions.
  Nature chemical biology 2009 Mandell DJ, Kortemme T
• Backbone flexibility in computational protein design.
  Current opinion in biotechnology 2009 Mandell DJ, Kortemme T
• Sub-angstrom accuracy in protein loop reconstruction by robotics-inspired conformational sampling.
  Nature methods 2009 Mandell DJ, Coutsias EA, Kortemme T
• Multi-constraint computational design suggests that native sequences of germline antibody H3 loops are nearly optimal for conformational flexibility.
  Proteins 2009 Babor M, Kortemme T
• A correspondence between solution-state dynamics of an individual protein and the sequence and conformational diversity of its family.
  PLoS computational biology 2009 Friedland GD, Lakomek NA, Griesinger C, Meiler J, Kortemme T
• Complex topology rather than complex membership is a determinant of protein dosage sensitivity.
  Molecular systems biology 2009 Oberdorf R, Kortemme T
• Outcome of a workshop on applications of protein models in biomedical research.
  Structure (London, England : 1993) 2009 Schwede T, Sali A, Honig B, Levitt M, Berman HM, Jones D, Brenner SE, Burley SK, Das R, Dokholyan NV, Dunbrack RL, Fidelis K, Fiser A, Godzik A, Huang YJ, Humblet C, Jacobson MP, Joachimiak A, Krystek…
• Differences in flexibility underlie functional differences in the Ras activators son of sevenless and Ras guanine nucleotide releasing factor 1.
  Structure (London, England : 1993) 2009 Freedman TS, Sondermann H, Kuchment O, Friedland GD, Kortemme T, Kuriyan J
• SAT-based Protein Design
  2009 IEEE/ACM International Conference on Computer-Aided Design Digest of Technical Papers (ICCAD 2009) 2009 Ollikainen N, Sentovich E, Coelho C, Kuehlmann A, Kortemme T
• Prediction of protein-protein interface sequence diversity using flexible backbone computational protein design.
  Structure (London, England : 1993) 2008 Humphris EL, Kortemme T
• Engineered protein connectivity to actin mimics PDZ-dependent recycling of G protein-coupled receptors but not its regulation by Hrs.
  The Journal of biological chemistry 2008 Lauffer BE, Chen S, Melero C, Kortemme T, von Zastrow M, Vargas GA
• Backrub-like backbone simulation recapitulates natural protein conformational variability and improves mutant side-chain prediction.
  Journal of molecular biology 2008 Smith CA, Kortemme T
• A simple model of backbone flexibility improves modeling of side-chain conformational variability.
  Journal of molecular biology 2008 Friedland GD, Linares AJ, Smith CA, Kortemme T
• A new twist in TCR diversity revealed by a forbidden alphabeta TCR.
  Journal of molecular biology 2007 McBeth C, Seamons A, Pizarro JC, Fleishman SJ, Baker D, Kortemme T, Goverman JM, Strong RK
• Structural mapping of protein interactions reveals differences in evolutionary pressures correlated to mRNA level and protein abundance.
  Structure (London, England : 1993) 2007 Eames M, Kortemme T
• Mutations designed to destabilize the receptor-bound conformation increase MICA-NKG2D association rate and affinity.
  The Journal of biological chemistry 2007 Lengyel CS, Willis LJ, Mann P, Baker D, Kortemme T, Strong RK, McFarland BJ
• Design of multi-specificity in protein interfaces.
  PLoS computational biology 2007 Humphris EL, Kortemme T
• A Ras-induced conformational switch in the Ras activator Son of sevenless.
  Proceedings of the National Academy of Sciences of the United States of America 2006 Freedman TS, Sondermann H, Friedland GD, Kortemme T, Bar-Sagi D, Marqusee S, Kuriyan J
• Structural basis for unique mechanisms of folding and hemoglobin binding by a malarial protease.
  Proceedings of the National Academy of Sciences of the United States of America 2006 Wang SX, Pandey KC, Somoza JR, Sijwali PS, Kortemme T, Brinen LS, Fletterick RJ, Rosenthal PJ, McKerrow JH
• Computational design of a new hydrogen bond network and at least a 300-fold specificity switch at a protein-protein interface.
  Journal of molecular biology 2006 Joachimiak LA, Kortemme T, Stoddard BL, Baker D
• Ca2+ indicators based on computationally redesigned calmodulin-peptide pairs.
  Chemistry & biology 2006 Palmer AE, Giacomello M, Kortemme T, Hires SA, Lev-Ram V, Baker D, Tsien RY
• Rational design of intercellular adhesion molecule-1 (ICAM-1) variants for antagonizing integrin lymphocyte function-associated antigen-1-dependent adhesion.
  The Journal of biological chemistry 2005 Song G, Lazar GA, Kortemme T, Shimaoka M, Desjarlais JR, Baker D, Springer TA
• A "solvated rotamer" approach to modeling water-mediated hydrogen bonds at protein-protein interfaces.
  Proteins 2005 Jiang L, Kuhlman B, Kortemme T, Baker D
• Potential functions for hydrogen bonds in protein structure prediction and design.
  Advances in protein chemistry 2005 Morozov AV, Kortemme T
• A new hydrogen-bonding potential for the design of protein-RNA interactions predicts specific contacts and discriminates decoys.
  Nucleic acids research 2004 Chen Y, Kortemme T, Robertson T, Baker D, Varani G
• Close agreement between the orientation dependence of hydrogen bonds observed in protein structures and quantum mechanical calculations.
  Proceedings of the National Academy of Sciences of the United States of America 2004 Morozov AV, Kortemme T, Tsemekhman K, Baker D
• Computational redesign of protein-protein interaction specificity.
  Nature structural & molecular biology 2004 Kortemme T, Joachimiak LA, Bullock AN, Schuler AD, Stoddard BL, Baker D
• Contributions of amino acid side chains to the kinetics and thermodynamics of the bivalent binding of protein L to Ig kappa light chain.
  Biochemistry 2004 Svensson HG, Wedemeyer WJ, Ekstrom JL, Callender DR, Kortemme T, Kim DE, Sjöbring U, Baker D
• Computational alanine scanning of protein-protein interfaces.
  Science's STKE : signal transduction knowledge environment 2004 Kortemme T, Kim DE, Baker D
• Computational design of protein-protein interactions.
  Current opinion in chemical biology 2004 Kortemme T, Baker D
• Evaluation of Models of Electrostatic Interactions in Proteins
  J. Phys. Chem. B 2003 Morozov AV, Kortemme T, Baker D
• Convergent mechanisms for recognition of divergent cytokines by the shared signaling receptor gp130.
  Molecular cell 2003 Boulanger MJ, Bankovich AJ, Kortemme T, Baker D, Garcia KC
• Protein-protein docking predictions for the CAPRI experiment.
  Proteins 2003 Gray JJ, Moughon SE, Kortemme T, Schueler-Furman O, Misura KM, Morozov AV, Baker D
• Symmetry recognizing asymmetry: analysis of the interactions between the C-type lectin-like immunoreceptor NKG2D and MHC class I-like ligands.
  Structure (London, England : 1993) 2003 McFarland BJ, Kortemme T, Yu SF, Baker D, Strong RK
• An orientation-dependent hydrogen bonding potential improves prediction of specificity and structure for proteins and protein-protein complexes.
  Journal of molecular biology 2003 Kortemme T, Morozov AV, Baker D
• A simple physical model for binding energy hot spots in protein-protein complexes.
  Proceedings of the National Academy of Sciences of the United States of America 2002 Kortemme T, Baker D
• Design, activity, and structure of a highly specific artificial endonuclease.
  Molecular cell 2002 Chevalier BS, Kortemme T, Chadsey MS, Baker D, Monnat RJ, Stoddard BL
• Simple physical models connect theory and experiment in protein folding kinetics.
  Journal of molecular biology 2002 Alm E, Morozov AV, Kortemme T, Baker D
• Similarities between the spectrin SH3 domain denatured state and its folding transition state.
  Journal of molecular biology 2000 Kortemme T, Kelly MJ, Kay LE, Forman-Kay J, Serrano L
• The design of linear peptides that fold as monomeric beta-sheet structures.
  Current opinion in structural biology 1999 Lacroix E, Kortemme T, Lopez de la Paz M, Serrano L
• Beta-hairpin and beta-sheet formation in designed linear peptides.
  Bioorganic & medicinal chemistry 1999 Ramírez-Alvarado M, Kortemme T, Blanco FJ, Serrano L
• Design of a 20-amino acid, three-stranded beta-sheet protein.
  Science (New York, N.Y.) 1998 Kortemme T, Ramírez-Alvarado M, Serrano L
• Ionization-reactivity relationships for cysteine thiols in polypeptides.
  Biochemistry 1998 Bulaj G, Kortemme T, Goldenberg DP
• Electrostatic interactions in the active site of the N-terminal thioredoxin-like domain of protein disulfide isomerase.
  Biochemistry 1996 Kortemme T, Darby NJ, Creighton TE
• Comparison of the (30-51, 14-38) two-disulphide folding intermediates of the homologous proteins dendrotoxin K and bovine pancreatic trypsin inhibitor by two-dimensional 1H nuclear magnetic resonance.
  Journal of molecular biology 1996 Kortemme T, Hollecker M, Kemmink J, Creighton TE
• Ionisation of cysteine residues at the termini of model alpha-helical peptides. Relevance to unusual thiol pKa values in proteins of the thioredoxin family.
  Journal of molecular biology 1995 Kortemme T, Creighton TE
• Helix propensities of the amino acids measured in alanine-based peptides without helix-stabilizing side-chain interactions.
  Protein science : a publication of the Protein Society 1994 Chakrabartty A, Kortemme T, Baldwin RL
• Aromatic side-chain contribution to far-ultraviolet circular dichroism of helical peptides and its effect on measurement of helix propensities.
  Biochemistry 1993 Chakrabartty A, Kortemme T, Padmanabhan S, Baldwin RL