Jiankun Lyu, Nicholas Kapolka, Ryan Gumpper, Assaf Alon, Liang Wang, Manish K. Jain, Ximena Barros-Álvarez, Kensuke Sakamoto, Yoojoong Kim, Jeffrey DiBerto, Kuglae Kim, Isabella S. Glenn, Tia A. Tummino, Sijie Huang, John J. Irwin, Olga O. Tarkhanova, Yurii Moroz, Georgios Skiniotis, Andrew C. Kruse, Brian K. Shoichet, Bryan L. Roth.
AlphaFold2 structures guide prospective ligand discovery
Science 2024 May Science0,eadn6354DOI:10.1126/science.adn6354
Xu P, Huang S, Krumm BE, Zhuang Y, Mao C, Zhang Y, Wang Y, Huang XP, Liu YF, He X, Li H, Yin W, Jiang Y, Zhang Y, Roth BL , Xu HE.
Structural genomics of the human dopamine receptor system
Cell Res. 2023 Aug;33(8):604-616. doi: 10.1038/s41422-023-00808-0. Epub 2023 May 23.
Brian E. Krumm, Jeffrey F. DiBerto, Reid H. J. Olsen, Hye Jin Kang, Samuel T. Slocum,
Shicheng Zhang, Ryan T. Strachan, Xi-Ping Huang, Lauren M. Slosky, Anthony B. Pinkerton,
Lawrence S. Barak, Marc G. Caron, Terry Kenakin*, Jonathan F. Fay, and Bryan L. Roth.
Neurotensin Receptor Allosterism Revealed in Complex with a Biased Allosteric Modulator
ACS. 2023 Mar 14.
Yue Wang, Youwen Zhuang, Jeffrey F DiBerto, X Edward Zhou, Gavin P Schmitz, Qingning Yuan, Manish K Jain, Weiyi Liu,
Karsten Melcher, Yi Jiang, Bryan L. Roth, H Eric Xu.
Structures of the entire human opioid receptor family.
Cell. 2023 Jan 11;S0092-8674(22)01545-8. doi: 10.1016/j.cell.2022.12.026. Online ahead of print.
Yongfeng Liu, Can Cao, Xi-Ping Huang, Ryan H Gumpper, Moira M Rachman, Sheng-Luen Shih, Brian E Krumm, Shicheng Zhang,
Brian K Shoichet, Jonathan F Fay, Bryan L. RothLigand recognition and allosteric modulation of the human MRGPRX1 receptorNat Chem Biol. 2022 Oct 27. doi: 10.1038/s41589-022-01173-6. Online ahead of print.
Can Cao, Ximena Barros-Álvarez, Shicheng Zhang, Kuglae Kim, Marc A Dämgen, Ouliana Panova 2,
Carl-Mikael Suomivuori, Jonathan F Fay, Xiaofang Zhong, Brian E Krumm, Ryan H Gumpper,
Alpay B Seven, Michael J Robertson, Nevan J Krogan, Ruth Hüttenhain, David E Nichols, Ron O Dror,
Georgios Skiniotis, Bryan L. RothSignaling snapshots of a serotonin receptor activated by the prototypical psychedelic LSDNeuron. 2022 Oct 5;110(19):3154-3167.e7. doi: 10.1016/j.neuron.2022.08.006. Epub 2022 Sep 9.
Anat Levit Kaplan, Danielle N Confair, Kuglae Kim, Ximena Barros-Álvarez, Ramona M Rodriguiz, Ying Yang, Oh Sang Kweon,
Tao Che, John D McCorvy, David N Kamber, James P Phelan, Luan Carvalho Martins, Vladimir M Pogorelov, Jeffrey F DiBerto,
Samuel T Slocum, Xi-Ping Huang, Jain Manish Kumar, Michael J Robertson, Ouliana Panova, Alpay B Seven, Autumn Q Wetsel,
William C Wetsel, John J Irwin, Georgios Skiniotis, Brian K Shoichet, Bryan L Roth, Jonathan A Ellman
Bespoke library docking for 5-HT2A receptor agonists with antidepressant activityNature. 2022 Sep 28. doi: 10.1038/s41586-022-05258-z. Online ahead of print.
Shicheng Zhang, He Chen, Chengwei Zhang, Ying Yang, Petr Popov, Jing Liu, Brian E Krumm, Can Cao, Kuglae Kim, Yan Xiong, Vsevolod Katritch,
Brian K Shoichet, Jian Jin, Jonathan F Fay, Bryan L. RothInactive and active state structures template selective tools for the human 5-HT 5A receptorNat Struct Mol Biol. 2022 Jul;29(7):677-687. doi: 10.1038/s41594-022-00796-6. Epub 2022 Jul 14.
Arman A Sadybekov, Anastasiia V Sadybekov, Yongfeng Liu, Christos Iliopoulos-Tsoutsouvas, Xi-Ping Huang, Julie Pickett,
Blake Houser, Nilkanth Patel, Ngan K Tran, Fei Tong, Nikolai Zvonok, Manish K Jain, Olena Savych, Dmytro S Radchenko,
Spyros P Nikas, Nicos A Petasis, Yurii S Moroz, Bryan L Roth, Alexandros Makriyannis, Vsevolod Katritch
Synthon-based ligand discovery in virtual libraries of over 11 billion compounds Nature. 2022 January;601(7893):452-459.doi: 10.1038/s41586-021-04220-9. Epub 2021 Dec 15.
2021
Can Cao, Hye Jin Kang, Isha Singh, He Chen, Chengwei Zhang, Wenlei Ye, Byron W. Hayes, Jing Liu, Ryan H. Gumpper, Brian J. Bender,
Samuel T. Slocum, Brian E. Krumm, Katherine Lansu, John D. McCorvy, Wesley K. Kroeze, Justin G. English, Jeffrey F. DiBerto,
Reid H. J. Olsen, Xi-Ping Huang, Shicheng Zhang, Yongfeng Liu, Kuglae Kim, Joel Karpiak, Lily Y. Jan, Soman N. Abraham, Jian Jin,
Brian K. Shoichet, Jonathan F. Fay & Bryan L. RothStructure, function and pharmacology of human itch GPCRsNature. 2021 November 17.
Zhuang Y, Xu P, Mao C, Wang L, Krumm B, Zhou XE, Huang S, Liu H, Cheng X, Huang XP, Shen DD, Xu T, Liu YF, Wang Y, Guo J, Jiang Y,
Jiang H, Melcher K, Roth BL, Zhang Y, Zhang C, Xu HE.
Structural insights into the human D1 and D2 dopamine receptor signaling complexes Cell. 2021 Feb 18;184(4):931-942.e18. doi: 10.1016/j.cell.2021.01.027. Epub 2021 Feb 10.
Peiyu Xu, Sijie Huang, Chunyou Mao, Brian E Krumm, X Edward Zhou, Yangxia Tan, Xi-Ping Huang,
Yongfeng Liu, Dan-Dan Shen, Yi Jiang, Xuekui Yu, Hualiang Jiang, Karsten Melcher, Bryan L Roth, Xi Cheng, Yan Zhang, H Eric Xu
Structures of the human dopamine D3 receptor-Gi complexes. Mol Cell. 2021 Jan 27:S1097-2765(21)00003-4. doi: 10.1016/j.molcel.2021.01.003.
2020
Kuglae Kim, Tao Che, Ouliana Panova, Jeffrey F DiBerto, Jiankun Lyu, Brian E Krumm,
Daniel Wacker, Michael J Robertson, Alpay B Seven, David E Nichols, Brian K Shoichet,
Georgios Skiniotis, Roth BLStructure of a Hallucinogen-Activated Gq-Coupled 5-HT 2A Serotonin Receptor Cell. 2020 Sep 17;182(6):1574-1588.e19. doi: 10.1016/j.cell.2020.08.024.
Pottel J, Armstrong D, Zou L, Fekete A, Huang XP, Torosyan H, Bednarczyk D, Whitebread S, Bhhatarai B, Liang G, Jin H, Ghaemi SN, Slocum S,
Lukacs KV, Irwin JJ, Berg EL, Giacomini KM, Roth BL, Shoichet BK, Urban L
The activities of drug inactive ingredients on biological targets. Science.. 2020 Jul 24;369(6502):403-413. doi: 10.1126/science.aaz9906.
Nagai Y, Miyakawa N, Takuwa H1, Hori Y, Oyama K, Ji B, Takahashi M, Huang XP2, Slocum ST, DiBerto JF, Xiong Y, Urushihata T, Hirabayashi T, Fujimoto A,
Mimura K, English JG, Liu J, Inoue KI, Kumata K, Seki C, Ono M, Shimojo M, Zhang MR, Tomita Y, Nakahara J, Suhara T, Takada M, Higuchi M, Jin J, Roth BL,
Minamimoto T.
Deschloroclozapine, a potent and selective chemogenetic actuator enables rapid neuronal and behavioral modulations in mice and monkeys. Nature Neuroscience.. 2020 Jul 6. doi: 10.1038/s41593-020-0661-3. [Epub ahead of print]
Reid H. J. Olsen, Jeffrey F. DiBerto, Justin G. English, Alexis M. Glaudin, Brian E. Krumm, Samuel T. Slocum, Tao Che, Ariana C. Gavin, John D. McCorvy, Bryan L. Roth & Ryan T. Strachan
TRUPATH, an open-source biosensor platform for interrogating the GPCR transducerome Nature Chemical Biology.. 2020 May 04. DOI: https://doi.org/10.1038/s41589-020-0535-8
David E. Gordon, Gwendolyn M. Jang, Mehdi Bouhaddou, Jiewei Xu, Kirsten Obernier, Kris M. White, Matthew J. O’Meara, Veronica V. Rezelj, Jeffrey Z. Guo,
Danielle L. Swaney, Tia A. Tummino, Ruth Huettenhain, Robyn M. Kaake, Alicia L. Richards, Beril Tutuncuoglu, Helene Foussard, Jyoti Batra, Kelsey Haas,
Maya Modak, Minkyu Kim, Paige Haas, Benjamin J. Polacco, Hannes Braberg, Jacqueline M. Fabius, Manon Eckhardt, Margaret Soucheray, Melanie J. Bennett,
Merve Cakir, Michael J. McGregor, Qiongyu Li, Bjoern Meyer, Ferdinand Roesch, Thomas Vallet, Alice Mac Kain, Lisa Miorin, Elena Moreno, Zun Zar Chi Naing,
Yuan Zhou, Shiming Peng, Ying Shi, Ziyang Zhang, Wenqi Shen, Ilsa T. Kirby, James E. Melnyk, John S. Chorba, Kevin Lou, Shizhong A. Dai, Inigo Barrio-Hernandez,
Danish Memon, Claudia Hernandez-Armenta, Jiankun Lyu, Christopher J. P. Mathy, Tina Perica, Kala B. Pilla, Sai J. Ganesan, Daniel J. Saltzberg, Ramachandran Rakesh,
Xi Liu, Sara B. Rosenthal, Lorenzo Calviello, Srivats Venkataramanan, Jose Liboy-Lugo, Yizhu Lin, Xi-Ping Huang, YongFeng Liu, Stephanie A. Wankowicz, Markus Bohn,
Maliheh Safari, Fatima S. Ugur, Cassandra Koh, Nastaran Sadat Savar, Quang Dinh Tran, Djoshkun Shengjuler, Sabrina J Fletcher, Michael C. O’Neal, Yiming Cai,
Jason C. J. Chang, David J. Broadhurst, Saker Klippsten, Phillip P. Sharp, Nicole A. Wenzell, Duygu Kuzuoglu, Hao-Yuan Wang, Raphael Trenker, Janet M. Young, Devin A. Cavero,
Joseph Hiatt, Theodore L. Roth, Ujjwal Rathore, Advait Subramanian, Julia Noack, Mathieu Hubert, Robert M. Stroud, Alan D. Frankel, Oren S. Rosenberg, Kliment A Verba, David A. Agard,
Melanie Ott, Michael Emerman, Natalia Jura, Mark von Zastrow, Eric Verdin, Alan Ashworth, Olivier Schwartz, Christophe d’Enfert, Shaeri Mukherjee, Matt Jacobson, Harmit S. Malik,
Danica G. Fujimori, Trey Ideker, Charles S. Craik, Stephen N. Floor, James S. Fraser, John D. Gross, Andrej Sali, Bryan L. Roth, Davide Ruggero, Jack Taunton, Tanja Kortemme,
Pedro Beltrao, Marco Vignuzzi, Adolfo García-Sastre, Kevan M. Shokat, Brian K. Shoichet & Nevan J. Krogan
A SARS-CoV-2 protein interaction map reveals targets for drug repurposing Nature.. 2020 April 30. DOI: https://doi.org/10.1038/s41586-020-2286-9
Tao Che, Hustin English, Brian E. Krumm, Kuglae Kim, Els Pardon, Reid H. J. Olsen, Sheng Wang, Shicheng Zhang, Jeffrey F. DiBerto, Noah Sciaky, F Ivy Carroll, Jan Steyaert, Daniel Wacker & Bryan L. RothNanobody-enabled monitoring of kappa opioid receptor states Nature Communications.. 2020 March 02. DOI: https://doi.org/10.1038/s41467-020-14889-7
Reed M. Stein, Hye Jin Kang, John D. McCorvy, Grant C. Glatfelter, Anthony J. Jones, Tao Che, Samuel Slocum, Xi-Ping Huang, Olena Savych, Yurii S. Moroz, Benjamin Stauch, Linda C. Johansson, Vadim Cherezov, Terry Kenakin, John J. Irwin, Brian K. Shoicet*, Bryan L. Roth*, Margarita L. Dubocovich*
Virtual discovery of melatonin receptor ligands to modulate circadian rythms Nature.. 2020 February 10. DOI: https://doi.org/10.1038/s41586-020-2027-0
*=Co-corresponding authors
Justin G. English, Reid H.J. Olsen, Katherine Lansu, M. Patel, K. White, A.S. Cockrell, D. Singh, Ryan T. Strachan, Daniel Wacker, Bryan L. Roth VEGAS as a Platform for Facile Directed Evolution in Mammalian Cells Cell.. 2019 July 4. DOI:https://doi.org/10.1016/j.cell.2019.05.051
Stauch B, Johansson LC, McCorvy JD, Patel N, Han GW, Huang XP, Gati C, Batyuk A, Slocum ST, Ishchenko A, Brehm W, White TA, Michaelian N, Madsen C, Zhu L, Grant TD, Grandner JM, Shiriaeva A, Olsen RHJ, Tribo AR, Yous S, Stevens RC, Weierstall U, Katritch V, *Roth BL, *Liu W, *Cherezov V.
Structural basis of ligand recognition at the human MT1 melatonin receptor. Nature.. 2019 Apr 24. doi: 10.1038/s41586-019-1141-3. [Epub ahead of print]
*BLR, WL and VC corresponding authors.
Johansson LC, Stauch B, McCorvy JD, Han GW, Patel N, Huang XP, Batyuk A, Gati C, Slocum ST, Li C, Grandner JM, Hao S, Olsen RHJ, Tribo AR, Zaare S, Zhu L, Zatsepin NA, Weierstall U, Yous S, Stevens RC, Liu W, *Roth BL, *Katritch V, *Cherezov V.
XFEL structures of the human MT2 melatonin receptor reveal the basis of subtype selectivity. Nature.. 2019 Apr 24. doi: 10.1038/s41586-019-1144-0. [Epub ahead of print]
*BLR, VK and VC corresponding authors.
Julia Kozlitina , Davide Risso , Katherine Lansu, Reid Hans Johnson Olsen, Eduardo Sainz, Donata Luiselli, Arnab Barik, Carlos Frigerio-Domingues, Luca Pagani, Stephen Wooding, Thomas Kirchner, Ray Niaura, Bryan Roth, Dennis Drayna
An African-specific haplotype in MRGPRX4 is associated with menthol cigarette smoking PLOS Genetics February 15, 2019 https://doi.org/10.1371/journal.pgen.1007916
Jiankun Lyu, Sheng Wang, Trent E. Balius, Isha Singh, Anat Levit, Yurii S. Moroz, Matthew J. O’Meara, Tao Che, Enkhjargal Algaa, Kateryna Tolmachova, Andrey A. Tolmachev, *Brian K. Shoichet, *Bryan L. Roth and *John J. Irwin
Ultra-large library docking for discovering new chemotypes Nature 14 February 2019 https://doi.org/10.1038/s41586-019-0917-9
*=BKS, BLR, and JJI=co-corresponding authors
Yao Peng, John D. McCorvy, Kasper Harpsøe, Katherine Lansu, Shuguang Yuan, Petr Popov, Lu Qu, Mengchen Pu, Tao Che, Louise F. Nikolajsen, Xi-Ping Huang, Yiran Wu, Ling Shen, Walden E. Bjørn-Yoshimoto, Kang Ding, Daniel Wacker, Gye Won Han, Jianjun Cheng, Vsevolod Katritch, Anders A. Jensen, Michael A. Hanson, Suwen Zhao, David E. Gloriam, Bryan L. Roth, Raymond C. Stevens, Zhi-Jie Liu
5-HT2C Receptor Structures Reveal the Structural Basis of GPCR PolypharmacologyCell. 2018; DOI: https://doi.org/10.1016/j.cell.2018.01.001
Tao Che, Susruta Majumdar, Saheem A. Zaidi, Pauline Ondachi, John D. McCorvy, Sheng Wang, Philip D. Mosier, Rajendra Uprety, Eyal Vardy, Brian E. Krumm, Gye Won Han, Ming-Yue Lee, Els Pardon, Jan Steyaert, Xi-Ping Huang, Ryan T. Strachan, Alexandra R. Tribo, Gavril W. Pasternak, F. Ivy Carroll, Raymond C. Stevens, Vadim Cherezov, Vsevolod Katritch, Daniel Wacker, Bryan L. Roth. Structure of the Nanobody-Stabilized Active State of the Kappa Opioid ReceptorCell. DOI: http://dx.doi.org/10.1016/j.cell.2017.12.011
Daniel Wackerab, Sheng Wanga, John D. McCorvya, Robin M. Betz, A.J. Venkatakrishnan, Anat Levit, Katherine Lansu, Zachary L. Schools, Tao Che, David E. Nichols, Brian K. Shoichet, Ron O. Drorb, Bryan L. Rothbc a Co-first authors b Co-corresonding c Lead Contact Crystal Structure of an LSD-Bound Human Serotonin Receptor.Cell 2017 Jan 26;168(3):377-389.e12. doi: 10.1016/j.cell.2016.12.033.
Aashish Manglik, Henry Lin, Dipendra K. Aryal, John D. McCorvy, Daniela Dengler, Gregory Corder, Anat Levit, Ralf C. Kling, Viachaslau Bernat, Harald Hübner, Xi-Ping Huang, Maria F. Sassano, Patrick M. Giguère, Stefan Löber, Da Duan,Grégory Scherrer, Brian K. Kobilka*, Peter Gmeiner*, Bryan L. Roth* & Brian K. Shoichet*
* Co-corresponding authors Structure-based discovery of opioid analgesics with reduced side effects.Nature. 2016 Aug 17:1-6. doi: 10.1038/nature19112. [Epub ahead of print]
Stuckey JI, Dickson BM, Cheng N, Liu Y, Norris JL, Cholensky SH, Tempel W, Qin S, Huber KG, Sagum C, Black K, Li F, Huang XP, Roth BL, Baughman BM, Senisterra G, Pattenden SG, Vedadi M, Brown PJ, Bedford MT, Min J, Arrowsmith CH, James LI, Frye SV. A cellular chemical probe targeting the chromodomains of Polycomb repressive complex 1.Nat Chem Biol. 10.1038/nchembio.2007, 2016 Jan 25
2015
Xi-Ping Huang, Joel Karpiak, Wesley K. Kroeze, Hu Zhu, Xin Chen, Sheryl S. Moy, Kara A. Saddoris, Viktoriya D. Nikolova, Martilias S. Farrell, Sheng Wang, Thomas J. Mangano, Deepak A. Deshpande, Alice Jiang, Raymond B. Penn, Jian Jin, Beverly H. Koller, Terry Kenakin, Brian K. Shoichet & Bryan L. Roth.Allosteric ligands for the pharmacologically dark receptors GPR68 and GPR65Nature doi:10.1038/nature15699, 2015 Nov 09
Elkins JM, Fedele V, Szklarz M, Abdul Azeez KR, Salah E, Mikolajczyk J, Romanov S, Sepetov N, Huang XP, Roth BL, Al Haj Zen A, Fourches D, Muratov E, Tropsha A, Morris J, Teicher BA, Kunkel M, Polley E, Lackey KE, Atkinson FL, Overington JP, Bamborough P, Müller S, Price DJ, Willson TM, Drewry DH, Knapp S, Zuercher WJ.Comprehensive characterization of the Published Kinase Inhibitor Set.Nature Biotechnol, doi: 10.1038/nbt.3374, 2015 Oct 26
Arrowsmith CH, Audia JE, Austin C, Baell J, Bennett J, Blagg J, Bountra C, Brennan PE, Brown PJ, Bunnage ME, Buser-Doepner C, Campbell RM, Carter AJ, Cohen P, Copeland RA, Cravatt B, Dahlin JL, Dhanak D, Edwards AM, Frederiksen M, Frye SV, Gray N, Grimshaw CE, Hepworth D, Howe T, Huber KV, Jin J, Knapp S, Kotz JD, Kruger RG, Lowe D, Mader MM, Marsden B, Mueller-Fahrnow A, Müller S, O'Hagan RC, Overington JP, Owen DR, Rosenberg SH, Roth BL, Ross R, Schapira M, Schreiber SL, Shoichet B, Sundström M, Superti-Furga G, Taunton J, Toledo-Sherman L, Walpole C, Walters MA, Willson TM, Workman P, Young RN, Zuercher WJ.
The promise and peril of chemical probes.Nature Chem Biol., 11(8):536-41. doi: 10.1038/nchembio.1867, 2015 Aug.
Vardy E, Robinson JE, Li C, Olsen RH, DiBerto JF, Giguere PM, Sassano FM, Huang XP, Zhu H, Urban DJ, White KL, Rittiner JE, Crowley NA, Pleil KE, Mazzone CM, Mosier PD, Song J, Kash TL, Malanga CJ, Krashes MJ, Roth BL. A New DREADD facilitates the multiplexed chemogenetic interrogation of behavior.Neuron, 86: 936-46, 2015.
Fenalti G, Zatsepin NA, Betti C, Giguere P, Han GW, Ishchenko A, Liu W, Guillemyn K, Zhang H, James D, Wang D, Weierstall U, Spence JC, Boutet S, Messerschmidt M, Williams GJ, Gati C, Yefanov OM, White TA, Oberthuer D, Metz M, Yoon CH, Barty A, Chapman HN, Basu S, Coe J, Conrad CE, Fromme R, Fromme P, Tourwé D, Schiller PW, Roth BL, Ballet S, Katritch V, Stevens RC, Cherezov V. Structural basis for bifunctional peptide recognition at human δ-opioid receptor.Nature Struct Mol Bio. 22: 265-268, 2015
Wu H, Wacker D, Mileni M, Katritch V, Han GW, Vardy E, Liu W, Thompson AA, Huang XP, Carroll FI, Mascarella SW, Westkaemper RB, Mosier PD, Roth BL, Cherezov V and Stevens RC (2012) Structure of the human κ-opioid receptor in complex with JDTic.Nature 485: 327-332, 2012.