Publications

Wayment-Steele HK^#, Otten R^#, Pitsawong W^#, Ojoawo A^#, Glaser A, Calderone LA & Kern D. The conformational landscape of fold-switcher KaiB is tuned to the circadian rhythm timescale. bioRxiv 2024

Stadnicki EJ, Ludewig H, Ramasamy PK, Wang X, Qiao Y, Kern D & Bradshaw N. Dual-Action Kinase Inhibitors Control p38α MAP Kinase Threonine Dephosphorylation. bioRxiv 2024

Zhang Z, Wayment-Steele HK, Brixi G, Wang H, Dal Peraro M, Kern D & Ovchinnikov S. Protein language models learn evolutionary statistics of interacting sequence motifs. bioRxiv 2024

Wayment-Steele HK^#, Ojoawo A^#, Otten R, Apitz JM, Pitsawong W, Hoemberger M, Ovchinnikov S, Colwell L & Kern D. Predicting multiple conformations via sequence clustering and AlphaFold2. Nature 2023

Jara GE, Pontiggia F, Otten R, Agafonov RV, Marti MA & Kern D. Wide Trasition-State Ensemble as Key Component for Enzyme Catalysis. bioRxiv 2023

Kim C, Ludewig H, Hadzipasic A, Kutter S, Nguyen V & Kern D. A biophysical framework for double-drugging kinases. Proc. Natl. Acad. Sci. US 2023

Pitsawong W, Pádua RAP, Grant T, Hoemberger M, Otten R, Bradshaw N, Grigorieff N & Kern D. From primordial clocks to circadian oscillators. Nature 2023

Stiller JB, Otten R, Häussinger D, Rieder PS, Theobald DL & Kern D. Structure determination of high-energy states in a dynamic protein ensemble. Nature 2022

Otten R^#, Pádua RAP^#, Bunzel HA^#, Nguyen V, Pitsawong W, Patterson M, Sui S, Perry SL, Cohen AE, Hilvert D & Kern D. How directed evolution reshapes the energy landscape in an enzyme to boost catalysis. Science 2020

Hoemberger M, Pitsawong W & Kern D. Cumulative mechanism of several major imatinib-resistant mutations in Abl kinase. PNAS 2020

Hadzipasic A, Wilson C, Nguyen V, Kern N, Kim C, Pitsawong W, Villali J, Zheng Y & Kern D. Ancient origins of allosteric activation in a Ser-Thr kinase. Science 2020

Zorba A^#, Nguyen V^#, Koide A, Hoemberger M, Zheng Y, Kutter S, Kim C, Koide S & Kern D. Allosteric Modulation of a Human Protein Kinase with Monobodies. Proc. Natl. Acad. Sci. USA 2019

Stiller JB^#, Kerns SJ^#, Hoemberger M, Cho Y-J, Otten R, Hagan MF & Kern D. Probing the Transition State in Enzyme Catalysis by High-Pressure NMR Dynamics. Nat. Catal. 2019

Pádua RAP^#, Sun Y^#, Marko I, Pitsawong W, Stiller JB, Otten R & Kern D. Mechanism of Activating Mutations and Allosteric Drug Inhibition of the Phosphatase SHP2. Nat. Commun. 2018

Pitsawong W^#, Buosi V^#, Otten R^#, Agafonov RV^#, Zorba A, Kern N, Kutter S, Kern G, Pádua RAP, Meniche X & Kern D. Dynamics of Human Protein Kinase Aurora A Linked to Drug Selectivity. eLife 2018

Otten R^#, Liu L^#, Kenner LR, Clarkson MW, Mavor D, Tawfik DS, Kern D & Fraser JS. Rescue of Conformational Dynamics in Enzyme Catalysis by Directed Evolution. Nat. Commun. 2018

Nguyen V^#, Wilson C^#, Hoemberger M, Stiller JB, Agafonov RV, Kutter S, English J, Theobald D & Kern D. Evolutionary Drivers of Thermoadaptation in Enzyme Catalysis. Science 2017

Chakrabarti KS^#, Agafonov RV^#, Pontiggia F, Otten R, Higgins MK, Schertler GF, Oprian DD & Kern D. Conformational Selection in a Protein-Protein Interaction Revealed by Dynamic Pathway Analysis. Cell Reports 2016

Wilson C, Agafonov RV & Kern D. Drug targets evolve, and so should the methods. Mol. Cell Oncol. 2016

Eichner T, Kutter S, Labeikovsky W, Buosi V & Kern D. Molecular Mechanism of Pin1-Tau Recognition and Catalysis. J. Mol. Biol. 2016

Kutter S, Eichner T, Deaconescu AM & Kern D. Regulation of Microtubule Assembly by Tau and not by Pin1. J. Mol. Biol. 2016

Pontiggia F, Pachov DV, Clarkson MW, Villali J, Hagan MF, Pande VS & Kern D. Free energy landscape of activation in a signaling protein at atomic resolution. Nat. Commun. 2015

Agafonov RV, Wilson C & Kern D. Evolution and intelligent design in drug development. Front. Mol. Biosci. 2015

Wilson C^#, Agafonov RV^#, Hoemberger M, Kutter S, Zorba A, Halpin J, Buosi V, Otten R, Waterman D, Theobald DL & Kern D. Using ancient protein kinases to unravel a modern cancer drug’s mechanism. Science 2015

Kerns SJ^#, Agafonov RV^#, Cho YJ^#, Pontiggia F, Otten R, Pachov DV, Kutter S, Phung LA, Murphy PN, Thai V, Alber T, Hagan MF & Kern D. The energy landscape of adenylate kinase during catalysis. Nat. Struct. Mol. Biol. 2015

Hass MA, Liu WM, Agafonov R.V., Otten R, Phung LA, Schilder JT, Kern D & Ubbink M. A minor conformation of a lanthanide tag on adenylate kinase characterized by paramagnetic relaxation dispersion NMR spectroscopy. J. Biomol. NMR 2015

Agafonov RV^#, Wilson C^#, Otten R, Buosi V & Kern D. Energetic dissection of Gleevec’s selectivity toward human tyrosine kinases. Nat. Struct. Mol. Biol. 2014

Zorba A^#, Buosi V^#, Kutter S, Kern N, Pontiggia F, Cho YJ & Kern D. Molecular mechanism of Aurora A kinase autophosphorylation and its allosteric activation by TPX2. eLife 2014

Villali J, Pontiggia F, Clarkson MW, Hagan MF & Kern D. Evidence against the “Y-T coupling” mechanism of activation in the response regulator NtrC. J. Mol. Biol. 2014

Ranaghan MJ, Kumar RP, Chakrabarti KS, Buosi V, Kern D & Oprian DD. A Highly Conserved Cysteine of Neuronal Calcium-sensing Proteins Controls Cooperative Binding of Ca²⁺ to Recoverin. J. Biol. Chem. 2013

Park JM, Hu J-H, Milshteyn A, Zhang, P-W, Moore CG, Park S, Datko MC, Doming RD, Reyes CM, Wang XJ, Etzkorn FA, Xiao B, Szumlinski KK, Kern D, Linden DJ & Worley PF. A Prolyl-isomerase Mediates Dopamine-dependent Plasticity and Cocaine Motor Sensitization. Cell 2013

Morrison EA, DeKoster GT, Dutta S, Vafabakhsh R, Clarkson MW, Bahl A, Kern D, Ha T & Henzler-Wildman KA. Antiparallel EmrE exports drugs by exchanging between asymmetric structures. Nature 2012

Otten R, Villali J, Kern D & Mulder FAA. Probing Microsecond Time Scale Dynamics in Proteins by Methyl ¹H Carr−Purcell−Meiboom−Gill Relaxation Dispersion NMR Measurements. Application to Activation of the Signaling Protein NtrC^r. J. Am. Chem. Soc. 2010

Villali J & Kern D. Choreographing an enzyme’s dance. Curr. Opin. Chem. Biol. 2010

Gardino AK, Villali J, Kivenson A, Lei M, Liu CF, Steindel P, Eisenmesser EZ, Labeikovsky W, Wolf-Watz M, Clarkson MW & Kern D. Transient Non-native Hydrogen Bonds Promote Activation of a Signaling Protein. Cell 2009

Fraser JS, Clarkson MW, Degnan SC, Erion R, Kern D & Alber T. Hidden alternative structures of proline isomerase essential for catalysis. Nature 2009

Shim S, Yuan JP, Kim JY, Zeng W, Huang G, Milshteyn A, Kern D, Muallem S, Ming G-L & Worley PF. Peptidyl-Prolyl Isomerase FKBP52 Controls Chemotropic Guidance of Neuronal Growth Cones via Regulation of TRPC1 Channel Opening. Neuron 2009

Clarkson MW, Lei M, Eisenmesser EZ, Labeikovsky W, Redfield A & Kern D. Mesodynamics in the SARS nucleocapsid measured by NMR field cycling. J. Biomol. NMR 2009

Lei M, Velos J, Gardino A, Kivenson A, Karplus M & Kern D. Segmented Transition Pathway of the Signaling Protein Nitrogen Regulatory Protein C. J. Mol. Biol. 2009

Thai V, Renesto P, Fowler CA, Brown DJ, Davis T, Gu W, Pollock DD, Kern D, Raoult D & Eisenmesser EZ. Structural, Biochemical, and in Vivo Characterization of the First Virally Encoded Cyclophilin from the Mimivirus. J. Mol. Biol. 2008

Henzler-Wildman KA & Kern D. Dynamic personalities of proteins. Nature 2007

Henzler-Wildman KA, Vu T, Lei M, Ott M, Wolf-Watz M, Fenn T, Pozharski E, Wilson MA, Petsko GA, Karplus M, Hübner CG & Kern D. Intrinsic motions along an enzymatic reaction trajectory. Nature 2007

Henzler-Wildman KA, Lei M, Thai V, Kerns SJ, Karplus M & Kern D. A hierarchy of timescales in protein dynamics is linked to enzyme catalysis. Nature 2007

Gardino AK & Kern D. Functional Dynamics of Response Regulators Using NMR Relaxation Techniques. Methods Enzymol. 2007

Labeikovsky W, Eisenmesser EZ, Bosco DA & Kern D. Structure and Dynamics of Pin1 During Catalysis by NMR. J. Mol. Biol. 2007

Wemmer DE & Kern D. Beryllofluoride Binding Mimics Phosphorylation of Aspartate in Response Regulators. J. Bacteriol. 2005

Eisenmesser EZ, Millet O, Labeikovsky W, Korzhnev DM, Wolf-Watz M, Bosco DA, Skalicky JJ, Kay LE & Kern D. Intrinsic dynamics of an enzyme underlies catalysis. Nature 2005

Tittmann K, Neef H, Golbik R, Hübner G & Kern D. Kinetic Control of Thiamin Diphosphate Activation in Enzymes Studied by Proton-Nitrogen Correlated NMR Spectroscopy. Biochemistry 2005

Kern D, Eisenmesser EZ & Wolf-Watz M. Enzyme Dynamics During Catalysis Measured by NMR Spectroscopy. Methods Enzymol. 2005

Wolf-Watz M, Thai V, Henzler-Wildman KA, Hadjipavlou G, Eisenmesser EZ & Kern D. Linkage between dynamics and catalysis in a thermophilic-mesophilic enzyme pair. Nat. Struct. Mol. Biol. 2004

Bosco DA & Kern D. Catalysis and Binding of Cyclophilin A with Different HIV-1 Capsid Constructs. Biochemistry 2004

Kern D & Zuiderweg ERP. The role of dynamics in allosteric regulation. Curr. Opin. Struct. Biol. 2003

Gardino AK, Volkman BF, Cho HS, Lee S-Y, Wemmer DE & Kern D. The NMR Solution Structure of BeF^3--Activated Spo0F Reveals the Conformational Switch in a Phosphorelay System. J. Mol. Biol. 2003

Kern D. Cutting the leash. Nat. Struct. Biol. 2002

Bosco DA, Eisenmesser E, Pochapsky S, Sundquist WI & Kern D. Catalysis of cis/trans isomerization in native HIV-1 capsid by human cyclophilin A. Proc. Natl. Acad. Sci. USA 2002

Eisenmesser EZ, Bosco DA, Akke M & Kern D. Enzyme Dynamics During Catalysis. Science 2002

Kern G, Pelton J, Marqusee S & Kern D. Structural properties of the histidine-containing loop in HIV-1 Rnase H. Biophys. Chem. 2002

Volkman BF, Lipson D, Wemmer DE & Kern D. Two-State Allosteric Behavior in a Single-Domain Signaling Protein. Science 2001

Kern D, Volkman BF, Luginbühl P, Nohaile MJ, Kustu S & Wemmer DE. Structure of a transiently phosphorylated “switch” in bacterial signal transduction. Nature 1999

Kern D, Kern G, Neef H, Tittmann K, Killenberg-Jabs M, Wikner C, Schneider G & Hübner G. How Thiamin Diphosphate is Activated in Enzymes. Science 1997