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Marginal specificity in protein interactions constrains evolution of a paralogous family

Ghose DA, Przydzial KE, Mahoney EM, Laub MT, Keating AE

Proc Natl Acad Sci. U S A. 2023

Peptides from human BNIP5 and PXT1 and non-native binders of pro-apoptotic BAK can directly activate or inhibit BAK-mediated membrane permeabilization

Aguilar F, Stacey Yu, Grant RA, Swanson S, Ghose D, Su BG, Sorosiek KA, Keating, AE

Structure 2023

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Neural network-derived Potts models for structure-based protein design using backbone atomic coordinates and tertiary motifs.

Li AJ, Lu M, Desta I, Sundar V, Grigoryan G, Keating AE

Protein Sci 2022

Molecular determinants of TRAF6 binding specificity suggest that native interaction partners are not optimized for affinity 

Halpin J, Whitney D, Rigoldi F, Sivaraman V, Singer A, Keating AE

Protein Sci 2022

Tertiary motifs as building blocks for the design of protein-binding peptides.

Swanson S. Sivarama V, Grigoryan G, Keating AE.

Protein Sci 2022

Native proline-rich motifs exploit sequence context to target actin-remodeling Ena/VASP proteins.

Hwang T, Grant RA, Ilunga MW, Sivaraman V, Keating AE. 

eLife. 2021

A distributed residue network permits conformational binding specificity in a conserved family of actin remodelers.

Hwang T, Parker S, Hill SM, Ilunga MW, Grant RA, Mouneimne G, Keating AE.

eLife. 2021 

Data-driven computational protein design.

Frappier V, Keating AE.

Curr Opin Struct Biol. 2021

Spatial Multiplexing of Fluorescent Reporters for Imaging Signaling Network Dynamics.

Linghu C, Johnson SL, Valdes PA, Shemesh OA, Park WM, Park D, Piatkevich KD, Wassie AT, Liu Y, An B, Barnes SA, Celiker OT, Yao CC, Yu CJ, Wang R, Adamala KP, Bear MF, Keating AE, Boyden ES.

Cell. 2020 

Precision Calcium Imaging of Dense Neural Populations via a Cell-Body-Targeted Calcium Indicator.

Shemesh OA, Linghu C, Piatkevich KD, Goodwin D, Celiker OT, Gritton HJ, Romano MF, Gao R, Yu CJ, Tseng HA, Bensussen S, Narayan S, Yang CT, Freifeld L, Siciliano CA, Gupta I, Wang J, Pak N, Yoon YG, Ullmann JFP, Guner-Ataman B, Noamany H, Sheinkopf ZR, Park WM, Asano S, Keating AE, Trimmer JS, Reimer J, Tolias AS, Bear MF, Tye KM, Han X, Ahrens MB, Boyden ES.

Neuron. 2020 

Tertiary Structural Motif Sequence Statistics Enable Facile Prediction and Design of Peptides that Bind Anti-apoptotic Bfl-1 and Mcl-1.

Frappier V, Jenson JM, Zhou J, Grigoryan G, Keating AE.

Structure. 2019

Peptide design by optimization on a data-parameterized protein interaction landscape.

Jenson JM, Xue V, Stretz L, Mandal T, Reich LL, Keating AE.

Proc Natl Acad Sci. U S A. 2018

Iterative optimization yields Mcl-1-targeting stapled peptides with selective cytotoxicity to Mcl-1-dependent cancer cells.

Rezaei Araghi R, Bird GH, Ryan JA, Jenson JM, Godes M, Pritz JR, Grant RA, Letai A, Walensky LD, Keating AE.

Proc Natl Acad Sci. U S A. 2018

PixelDB: Protein-peptide complexes annotated with structural conservation of the peptide binding mode.

Frappier V, Duran M, Keating AE.

Protein Sci. 2018

Modular assembly of a protein nanotriangle using orthogonally interacting coiled coils.

Park WM, Bedewy M, Berggren KK, Keating AE.

Sci Rep. 2017

Epistatic mutations in PUMA BH3 drive an alternate binding mode to potently and selectively inhibit anti-apoptotic Bfl-1.

Jenson JM, Ryan JA, Grant RA, Letai A, Keating AE.

Elife. 2017


Combinatorial bZIP dimers display complex DNA-binding specificity landscapes.

Rodríguez-Martínez JA, Reinke AW, Bhimsaria D, Keating AE, Ansari AZ.

Elife. 2017


Enriching Peptide Libraries for Binding Affinity and Specificity Through Computationally Directed Library Design.

Foight GW, Chen TS, Richman D, Keating AE.

Methods Mol Biol. 2017

AB-Bind: Antibody binding mutational database for computational affinity predictions.

Sirin S, Apgar JR, Bennett EM, Keating AE.

Protein Sci. 2016

Designing helical peptide inhibitors of protein-protein interactions.

Rezaei Araghi R, Keating AE.

Curr Opin Struct Biol. 2016 


Designing helical peptide inhibitors of protein-protein interactions.

Rezaei Araghi R, Keating AE.

Curr Opin Struct Biol. 2016


Comparison of the peptide binding preferences of three closely related TRAF paralogs: TRAF2, TRAF3, and TRAF5.

Foight GW, Keating AE.

Protein Sci. 2016

Rapid Optimization of Mcl-1 Inhibitors using Stapled Peptide Libraries Including Non-Natural Side Chains.

Rezaei Araghi R, Ryan JA, Letai A, Keating AE.

ACS Chem Biol. 2016

The Orientations of Large Aspect-Ratio Coiled-Coil Proteins Attached to Gold Nanostructures.

Chang JB, Kim YH, Thompson E, No YH, Kim NH, Arrieta J, Manfrinato VR, Keating AE, Berggren KK.

Small. 2016

AB-Bind: Antibody binding mutational database for computational affinity predictions.

Sirin S, Apgar JR, Bennett EM, Keating AE.

Protein Sci. 2016

Selective peptide inhibitors of antiapoptotic cellular and viral Bcl-2 proteins lead to cytochrome c release during latent Kaposi's sarcoma-associated herpesvirus infection.

Burrer CM, Foight GW, Keating AE, Chan GC.

Virus Res. 2016

Generating High-Accuracy Peptide-Binding Data in High Throughput with Yeast Surface Display and SORTCERY.

Reich LL, Dutta S, Keating AE.

Methods Mol Biol. 2016

A Barcoding Strategy Enabling Higher-Throughput Library Screening by Microscopy.

Chen R, Rishi HS, Potapov V, Yamada MR, Yeh VJ, Chow T, Cheung CL, Jones AT, Johnson TD, Keating AE, DeLoache WC, Dueber JE.

ACS Synth Biol. 2015

Locating Herpesvirus Bcl-2 Homologs in the Specificity Landscape of Anti-Apoptotic Bcl-2 Proteins.

Foight GW, Keating AE.

J Mol Biol. 2015

SORTCERY-A High-Throughput Method to Affinity Rank Peptide Ligands.

Reich LL, Dutta S, Keating AE.

J Mol Biol. 2015

Potent and specific peptide inhibitors of human pro-survival protein Bcl-xL.

Dutta S, Ryan J, Chen TS, Kougentakis C, Letai A, Keating AE.

J Mol Biol. 2015 

Data-driven prediction and design of bZIP coiled-coil interactions.

Potapov V, Kaplan JB, Keating AE.

PLoS Comput Biol. 2015

Selectivity in subunit composition of Ena/VASP tetramers.

Riquelme DN, Meyer AS, Barzik M, Keating A, Gertler FB.

Biosci Rep. 2015

A set of computationally designed orthogonal antiparallel homodimers that expands the synthetic coiled-coil toolkit.

Negron C, Keating AE.

J Am Chem Soc. 2014 


Designed BH3 peptides with high affinity and specificity for targeting Mcl-1 in cells.

Foight GW, Ryan JA, Gullá SV, Letai A, Keating AE.

ACS Chem Biol. 2014 


Increasing the affinity of selective bZIP-binding peptides through surface residue redesign.

Kaplan JB, Reinke AW, Keating AE.

Protein Sci. 2014


Genome-wide prediction and validation of peptides that bind human prosurvival Bcl-2 proteins.

DeBartolo J, Taipale M, Keating AE.

PLoS Comput Biol. 2014


Networks of bZIP protein-protein interactions diversified over a billion years of evolution.

Reinke AW, Baek J, Ashenberg O, Keating AE.

Science. 2013


Peptide ligands for pro-survival protein Bfl-1 from computationally guided library screening.

Dutta S, Chen TS, Keating AE.

ACS Chem Biol. 2013 


Helix bundle loops determine whether histidine kinases autophosphorylate in cis or in trans.

Ashenberg O, Keating AE, Laub MT.

J Mol Biol. 2013

Structure-based redesign of the binding specificity of anti-apoptotic Bcl-x(L).

Chen TS, Palacios H, Keating AE.

J Mol Biol. 2013

Methods in Enzymology. Methods in protein design. Preface.

Keating AE.

Methods Enzymol. 2013

Multistate protein design using CLEVER and CLASSY.

Negron C, Keating AE.

Methods Enzymol. 2013

bZIP transcription factors affecting secondary metabolism, sexual development and stress responses in Aspergillus nidulans.

Yin WB, Reinke AW, Szilágyi M, Emri T, Chiang YM, Keating AE, Pócsi I, Wang CC, Keller NP.

Microbiology. 2013 

Predictive Bcl-2 family binding models rooted in experiment or structure.

DeBartolo J, Dutta S, Reich L, Keating AE.

J Mol Biol. 2012

In silico and in vitro elucidation of BH3 binding specificity toward Bcl-2.

London N, Gullá S, Keating AE, Schueler-Furman O.

Biochemistry. 2012

Designing specific protein-protein interactions using computation, experimental library screening, or integrated methods.

Chen TS, Keating AE.

Protein Sci. 2012

SYNZIP protein interaction toolbox: in vitro and in vivo specifications of heterospecific coiled-coil interaction domains.

Thompson KE, Bashor CJ, Lim WA, Keating AE.

ACS Synth Biol. 2012 

Determinants of homodimerization specificity in histidine kinases.

Ashenberg O, Rozen-Gagnon K, Laub MT, Keating AE.

J Mol Biol. 2011

Design of peptide inhibitors that bind the bZIP domain of Epstein-Barr virus protein BZLF1.

Chen TS, Reinke AW, Keating AE.

J Mol Biol. 2011

Protein binding specificity versus promiscuity.

Schreiber G, Keating AE.

Curr Opin Struct Biol. 2011 

Multicoil2: predicting coiled coils and their oligomerization states from sequence in the twilight zone.

Trigg J, Gutwin K, Keating AE, Berger B.

PLoS One. 2011

Identifying and reducing error in cluster-expansion approximations of protein energies.

Hahn S, Ashenberg O, Grigoryan G, Keating AE.

J Comput Chem. 2010 

The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer.

Stewart ML, Fire E, Keating AE, Walensky LD.

Nat Chem Biol. 2010

Determinants of BH3 binding specificity for Mcl-1 versus Bcl-xL.

Dutta S, Gullá S, Chen TS, Fire E, Grant RA, Keating AE.

J Mol Biol. 2010 

A synthetic coiled-coil interactome provides heterospecific modules for molecular engineering.

Reinke AW, Grant RA, Keating AE.

J Am Chem Soc. 2010

Specific coiled-coil interactions contribute to a global model of the structure of the spindle pole body.

Zizlsperger N, Keating AE.

J Struct Biol. 2010

Identification of bZIP interaction partners of viral proteins HBZ, MEQ, BZLF1, and K-bZIP using coiled-coil arrays.

Reinke AW, Grigoryan G, Keating AE.

Biochemistry. 2010 

Mcl-1-Bim complexes accommodate surprising point mutations via minor structural changes.

Fire E, Gullá SV, Grant RA, Keating AE.

Protein Sci. 2010

Cluster expansion models for flexible-backbone protein energetics.

Apgar JR, Hahn S, Grigoryan G, Keating AE.

J Comput Chem. 2009 

X-ray vs. NMR structures as templates for computational protein design.

Schneider M, Fu X, Keating AE.

Proteins. 2009 

A computationally guided protein-interaction screen uncovers coiled-coil interactions involved in vesicular trafficking.

Zhang H, Chen J, Wang Y, Peng L, Dong X, Lu Y, Keating AE, Jiang T.

J Mol Biol. 2009 

Design of protein-interaction specificity gives selective bZIP-binding peptides.

Grigoryan G, Reinke AW, Keating AE.

Nature. 2009 

Analysis of coiled-coil interactions between core proteins of the spindle pole body.

Zizlsperger N, Malashkevich VN, Pillay S, Keating AE.

Biochemistry. 2008

Predicting helix orientation for coiled-coil dimers.

Apgar JR, Gutwin KN, Keating AE.

Proteins. 2008

Structural specificity in coiled-coil interactions.

Grigoryan G, Keating AE.

Curr Opin Struct Biol. 2008

Computing van der Waals energies in the context of the rotamer approximation.

Grigoryan G, Ochoa A, Keating AE.

Proteins. 2007

Modeling backbone flexibility to achieve sequence diversity: the design of novel alpha-helical ligands for Bcl-xL.

Fu X, Apgar JR, Keating AE.

J Mol Biol. 2007

A rational route to probing membrane proteins.

Keating AE.

Genome Biol. 2007

Ultra-fast evaluation of protein energies directly from sequence.

Grigoryan G, Zhou F, Lustig SR, Ceder G, Morgan D, Keating AE.

PLoS Comput Biol. 2006


Structure-based prediction of bZIP partnering specificity.

Grigoryan G, Keating AE.

J Mol Biol. 2006

Paircoil2: improved prediction of coiled coils from sequence.

McDonnell AV, Jiang T, Keating AE, Berger B.

Bioinformatics. 2006


Orientation and oligomerization specificity of the Bcr coiled-coil oligomerization domain.

Taylor CM, Keating AE.

Biochemistry. 2005

Coarse-graining protein energetics in sequence variables.

Zhou F, Grigoryan G, Lustig SR, Keating AE, Ceder G, Morgan D.

Phys Rev Lett. 2005


AVID: an integrative framework for discovering functional relationships among proteins.

Jiang T, Keating AE.

BMC Bioinformatics. 2005

Design of a heterospecific, tetrameric, 21-residue miniprotein with mixed alpha/beta structure.

Ali MH, Taylor CM, Grigoryan G, Allen KN, Imperiali B, Keating AE.

Structure. 2005

Predicting specificity in bZIP coiled-coil protein interactions.

Fong JH, Keating AE, Singh M.

Genome Biol. 2004

Comprehensive identification of human bZIP interactions with coiled-coil arrays.

Newman JR, Keating AE.

Science. 2003

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