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AI is a viable alternative to high throughput screening: a 318-target study

Title:	AI is a viable alternative to high throughput screening: a 318-target study
Authors:	null, null; Wallach, Izhar; Bernard, Denzil; Nguyen, Kong; Ho, Gregory; Morrison, Adrian; Stecula, Adrian; Rosnik, Andreana; O'Sullivan, Ann Marie; Davtyan, Aram; Samudio, Ben; Thomas, Bill; Worley, Brad; Butler, Brittany; Laggner, Christian; Thayer, Desiree; Moharreri, Ehsan; Friedland, Greg; Truong, Ha; van den Bedem, Henry; Ng, Ho Leung; Stafford, Kate; Sarangapani, Krishna; Giesler, Kyle; Ngo, Lien; Mysinger, Michael; Ahmed, Mostafa; Anthis, Nicholas J.; Henriksen, Niel; Gniewek, Pawel; Eckert, Sam; de Oliveira, Saulo; Suterwala, Shabbir; PrasadPrasad, Srimukh Veccham Krishna; Shek, Stefani; Contreras, Stephanie; Hare, Stephanie; Palazzo, Teresa; O'Brien, Terrence E.; Van Grack, Tessa; Williams, Tiffany; Chern, Ting-Rong; Kenyon, Victor; Lee, Andreia H.; Cann, Andrew B.; Bergman, Bastiaan; Anderson, Brandon M.; Cox, Bryan D.; Warrington, Jeffrey M.; Sorenson, Jon M.; Goldenberg, Joshua M.; Young, Matthew A.; DeHaan, Nicholas; Pemberton, Ryan P.; Schroedl, Stefan; Abramyan, Tigran M.; Gupta, Tushita; Mysore, Venkatesh; Presser, Adam G.; Ferrando, Adolfo A.; Andricopulo, Adriano D.; Ghosh, Agnidipta; Ayachi, Aicha Gharbi; Mushtaq, Aisha; Shaqra, Ala M.; Toh, Alan Kie Leong; Smrcka, Alan V.; Ciccia, Alberto; de Oliveira, Aldo Sena; Sverzhinsky, Aleksandr; de Sousa, Alessandra Mara; Agoulnik, Alexander I.; Kushnir, Alexander; Freiberg, Alexander N.; Statsyuk, Alexander V.; Gingras, Alexandre R.; Degterev, Alexei; Tomilov, Alexey; Vrielink, Alice; Garaeva, Alisa A.; Bryant-Friedrich, Amanda; Caflisch, Amedeo; Patel, Amit K.; Rangarajan, Amith Vikram; Matheeussen, An; Battistoni, Andrea; Caporali, Andrea; Chini, Andrea; Ilari, Andrea; Mattevi, Andrea; Foote, Andrea Talbot; Trabocchi, Andrea; Stahl, Andreas; Herr, Andrew B.; Berti, Andrew; Freywald, Andrew; Reidenbach, Andrew G.; Lam, Andrew; Cuddihy, Andrew R.; White, Andrew; Taglialatela, Angelo; Ojha, Anil K.; Cathcart, Ann M.; Motyl, Anna A. L.; Borowska, Anna; D'Antuono, Anna; Hirsch, Anna K. H.; Porcelli, Anna Maria; Minakova, Anna; Montanaro, Anna; Müller, Anna; Fiorillo, Annarita; Virtanen, Anniina; O'Donoghue, Anthony J.; Del Rio Flores, Antonio; Garmendia, Antonio E.; Pineda-Lucena, Antonio; Panganiban, Antonito T.; Samantha, Ariela; Chatterjee, Arnab K.; Haas, Arthur L.; Paparella, Ashleigh S.; John, Ashley L. St.; Prince, Ashutosh; ElSheikh, Assmaa; Apfel, Athena Marie; Colomba, Audrey; O'Dea, Austin; Diallo, Bakary N'tji; Ribeiro, Beatriz Murta Rezende Moraes; Bailey-Elkin, Ben A.; Edelman, Benjamin L.; Liou, Benjamin; Perry, Benjamin; Chua, Benjamin Soon Kai; Kováts, Benjámin; Englinger, Bernhard; Balakrishnan, Bijina; Gong, Bin; Agianian, Bogos; Pressly, Brandon; Salas, Brenda P. Medellin; Duggan, Brendan M.; Geisbrecht, Brian V.; Dymock, Brian W.; Morten, Brianna C.; Hammock, Bruce D.; Mota, Bruno Eduardo Fernandes; Dickinson, Bryan C.; Fraser, Cameron; Lempicki, Camille; Novina, Carl D.; Torner, Carles; Ballatore, Carlo; Bon, Carlotta; Chapman, Carly J.; Partch, Carrie L.; Chaton, Catherine T.; Huang, Chang; Yang, Chao-Yie; Kahler, Charlene M.; Karan, Charles; Keller, Charles; Dieck, Chelsea L.; Huimei, Chen; Liu, Chen; Peltier, Cheryl; Mantri, Chinmay Kumar; Kemet, Chinyere Maat; Müller, Christa E.; Weber, Christian; Zeina, Christina M.; Muli, Christine S.; Morisseau, Christophe; Alkan, Cigdem; Reglero, Clara; Loy, Cody A.; Wilson, Cornelia M.; Myhr, Courtney; Arrigoni, Cristina; Paulino, Cristina; Santiago, César; Luo, Dahai; Tumes, Damon J.; Keedy, Daniel A.; Lawrence, Daniel A.; Chen, Daniel; Manor, Danny; Trader, Darci J.; Hildeman, David A.; Drewry, David H.; Dowling, David J.; Hosfield, David J.; Smith, David M.; Moreira, David; Siderovski, David P.; Shum, David; Krist, David T.; Riches, David W. H.; Ferraris, Davide Maria; Anderson, Deborah H.; Coombe, Deirdre R.; Welsbie, Derek S.; Hu, Di; Ortiz, Diana; Alramadhani, Dina; Zhang, Dingqiang; Chaudhuri, Dipayan; Slotboom, Dirk J.; Ronning, Donald R.; Lee, Donghan; Dirksen, Dorian; Shoue, Douglas A.; Zochodne, Douglas William; Krishnamurthy, Durga; Duncan, Dustin; Glubb, Dylan M.; Gelardi, Edoardo Luigi Maria; Hsiao, Edward C.; Lynn, Edward G.; Silva, Elany Barbosa; Aguilera, Elena; Lenci, Elena; Abraham, Elena Theres; Lama, Eleonora; Mameli, Eleonora; Leung, Elisa; Giles, Ellie; Christensen, Emily M.; Mason, Emily R.; Petretto, Enrico; Trakhtenberg, Ephraim F.; Rubin, Eric J.; Strauss, Erick; Thompson, Erik W.; Cione, Erika; Lisabeth, Erika Mathes; Fan, Erkang; Kroon, Erna Geessien; Jo, Eunji; García-Cuesta, Eva M.; Glukhov, Evgenia; Gavathiotis, Evripidis; Yu, Fang; Xiang, Fei; Leng, Fenfei; Wang, Feng; Ingoglia, Filippo; van den Akker, Focco; Borriello, Francesco; Vizeacoumar, Franco J.; Luh, Frank; Buckner, Frederick S.; Vizeacoumar, Frederick S.; Bdira, Fredj Ben; Svensson, Fredrik; Rodriguez, G. Marcela; Bognár, Gabriella; Lembo, Gaia; Zhang, Gang; Dempsey, Garrett; Eitzen, Gary; Mayer, Gaétan; Greene, Geoffrey L.; Garcia, George A.; Lukacs, Gergely L.; Prikler, Gergely; Parico, Gian Carlo G.; Colotti, Gianni; De Keulenaer, Gilles; Cortopassi, Gino; Roti, Giovanni; Girolimetti, Giulia; Fiermonte, Giuseppe; Gasparre, Giuseppe; Leuzzi, Giuseppe; Dahal, Gopal; Michlewski, Gracjan; Conn, Graeme L.; Stuchbury, Grant David; Bowman, Gregory R.; Popowicz, Grzegorz Maria; Veit, Guido; de Souza, Guilherme Eduardo; Akk, Gustav; Caljon, Guy; Alvarez, Guzmán; Rucinski, Gwennan; Lee, Gyeongeun; Cildir, Gökhan; Li, Hai; Breton, Hairol E.; Jafar-Nejad, Hamed; Zhou, Han; Moore, Hannah P.; Tilford, Hannah; Yuan, Haynes; Shim, Heesung; Wulff, Heike; Hoppe, Heinrich; Chaytow, Helena; Tam, Heng-Keat; Van Remmen, Holly; Xu, Hongyang; Debonsi, Hosana Maria; Lieberman, Howard B.; Jung, Hoyoung; Fan, Hua-Ying; Feng, Hui; Zhou, Hui; Kim, Hyeong Jun; Greig, Iain R.; Caliandro, Ileana; Corvo, Ileana; Arozarena, Imanol; Mungrue, Imran N.; Verhamme, Ingrid M.; Qureshi, Insaf Ahmed; Lotsaris, Irina; Cakir, Isin; Perry, J. Jefferson P.; Kwiatkowski, Jacek; Boorman, Jacob; Ferreira, Jacob; Fries, Jacob; Kratz, Jadel Müller; Miner, Jaden; Siqueira-Neto, Jair L.; Granneman, James G.; Ng, James; Shorter, James; Voss, Jan Hendrik; Gebauer, Jan M.; Chuah, Janelle; Mousa, Jarrod J.; Maynes, Jason T.; Evans, Jay D.; Dickhout, Jeffrey; MacKeigan, Jeffrey P.; Jossart, Jennifer N.; Zhou, Jia; Lin, Jiabei; Xu, Jiake; Wang, Jianghai; Zhu, Jiaqi; Liao, Jiayu; Xu, Jingyi; Zhao, Jinshi; Lin, Jiusheng; Lee, Jiyoun; Reis, Joana; Stetefeld, Joerg; Bruning, John B.; Bruning, John Burt; Coles, John G.; Tanner, John J.; Pascal, John M.; So, Jonathan; Pederick, Jordan L.; Costoya, Jose A.; Rayman, Joseph B.; Maciag, Joseph J.; Nasburg, Joshua Alexander; Gruber, Joshua J.; Finkelstein, Joshua M.; Watkins, Joshua; Rodríguez-Frade, José Miguel; Arias, Juan Antonio Sanchez; Lasarte, Juan José; Oyarzabal, Julen; Milosavljevic, Julian; Cools, Julie; Lescar, Julien; Bogomolovas, Julijus; Wang, Jun; Kee, Jung-Min; Liao, Junzhuo; Sistla, Jyothi C.; Abrahão, Jônatas Santos; Sishtla, Kamakshi; Francisco, Karol R.; Hansen, Kasper B.; Molyneaux, Kathleen A.; Cunningham, Kathryn A.; Martin, Katie R.; Gadar, Kavita; Ojo, Kayode K.; Wong, Keith S.; Wentworth, Kelly L.; Lai, Kent; Lobb, Kevin A.; Hopkins, Kevin M.; Parang, Keykavous; Machaca, Khaled; Pham, Kien; Ghilarducci, Kim; Sugamori, Kim S.; McManus, Kirk James; Musta, Kirsikka; Faller, Kiterie M. E.; Nagamori, Kiyo; Mostert, Konrad J.; Korotkov, Konstantin V.; Liu, Koting; Smith, Kristiana S.; Sarosiek, Kristopher; Rohde, Kyle H.; Kim, Kyu Kwang; Lee, Kyung Hyeon; Pusztai, Lajos; Lehtiö, Lari; Haupt, Larisa M.; Cowen, Leah E.; Byrne, Lee J.; Su, Leila; Wert-Lamas, Leon; Puchades-Carrasco, Leonor; Chen, Lifeng; Malkas, Linda H.; Zhuo, Ling; Hedstrom, Lizbeth; Walensky, Loren D.; Antonelli, Lorenzo; Iommarini, Luisa; Whitesell, Luke; Randall, Lía M.; Fathallah, M. Dahmani; Nagai, Maira Harume; Kilkenny, Mairi Louise; Ben-Johny, Manu; Lussier, Marc P.; Windisch, Marc P.; Lolicato, Marco; Lolli, Marco Lucio; Vleminckx, Margot; Caroleo, Maria Cristina; Macias, Maria J.; Valli, Marilia; Barghash, Marim M.; Mellado, Mario; Tye, Mark A.; Wilson, Mark A.; Hannink, Mark; Ashton, Mark R.; Cerna, Mark Vincent C. dela; Giorgis, Marta; Safo, Martin K.; Maurice, Martin St.; McDowell, Mary Ann; Pasquali, Marzia; Mehedi, Masfique; Serafim, Mateus Sá Magalhães; Soellner, Matthew B.; Alteen, Matthew G.; Champion, Matthew M.; Skorodinsky, Maxim; O'Mara, Megan L.; Bedi, Mel; Rizzi, Menico; Levin, Michael; Mowat, Michael; Jackson, Michael R.; Paige, Mikell; Al-Yozbaki, Minnatallah; Giardini, Miriam A.; Maksimainen, Mirko M.; De Luise, Monica; Hussain, Muhammad Saddam; Christodoulides, Myron; Stec, Natalia; Zelinskaya, Natalia; Van Pelt, Natascha; Merrill, Nathan M.; Singh, Nathanael; Kootstra, Neeltje A.; Singh, Neeraj; Gandhi, Neha S.; Chan, Nei-Li; Trinh, Nguyen Mai; Schneider, Nicholas O.; Matovic, Nick; Horstmann, Nicola; Longo, Nicola; Bharambe, Nikhil; Rouzbeh, Nirvan; Mahmoodi, Niusha; Gumede, Njabulo Joyfull; Anastasio, Noelle C.; Khalaf, Noureddine Ben; Rabal, Obdulia; Kandror, Olga; Escaffre, Olivier; Silvennoinen, Olli; Bishop, Ozlem Tastan; Iglesias, Pablo; Sobrado, Pablo; Chuong, Patrick; O'Connell, Patrick; Martin-Malpartida, Pau; Mellor, Paul; Fish, Paul V.; Moreira, Paulo Otávio Lourenço; Zhou, Pei; Liu, Pengda; Wu, Pengpeng; Agogo-Mawuli, Percy; Jones, Peter L.; Ngoi, Peter; Toogood, Peter; Ip, Philbert; von Hundelshausen, Philipp; Lee, Pil H.; Rowswell-Turner, Rachael B.; Balaña-Fouce, Rafael; Rocha, Rafael Eduardo Oliveira; Guido, Rafael V. C.; Ferreira, Rafaela Salgado; Agrawal, Rajendra K.; Harijan, Rajesh K.; Ramachandran, Rajesh; Verma, Rajkumar; Singh, Rakesh K.; Tiwari, Rakesh Kumar; Mazitschek, Ralph; Koppisetti, Rama K.; Dame, Remus T.; Douville, Renée N.; Austin, Richard C.; Taylor, Richard E.; Moore, Richard G.; Ebright, Richard H.; Angell, Richard M.; Yan, Riqiang; Kejriwal, Rishabh; Batey, Robert A.; Blelloch, Robert; Vandenberg, Robert J.; Hickey, Robert J.; Kelm, Robert J.; Lake, Robert J.; Bradley, Robert K.; Blumenthal, Robert M.; Solano, Roberto; Gierse, Robin Matthias; Viola, Ronald E.; McCarthy, Ronan R.; Reguera, Rosa Maria; Uribe, Ruben Vazquez; do Monte-Neto, Rubens Lima; Gorgoglione, Ruggiero; Cullinane, Ryan T.; Katyal, Sachin; Hossain, Sakib; Phadke, Sameer; Shelburne, Samuel A.; Geden, Sandra E.; Johannsen, Sandra; Wazir, Sarah; Legare, Scott; Landfear, Scott M.; Radhakrishnan, Senthil K.; Ammendola, Serena; Dzhumaev, Sergei; Seo, Seung-Yong; Li, Shan; Zhou, Shan; Chu, Shaoyou; Chauhan, Shefali; Maruta, Shinsaku; Ashkar, Shireen R.; Shyng, Show-Ling; Conticello, Silvestro G.; Buroni, Silvia; Garavaglia, Silvia; White, Simon J.; Zhu, Siran; Tsimbalyuk, Sofiya; Chadni, Somaia Haque; Byun, Soo Young; Park, Soonju; Xu, Sophia Q.; Banerjee, Sourav; Zahler, Stefan; Espinoza, Stefano; Gustincich, Stefano; Sainas, Stefano; Celano, Stephanie L.; Capuzzi, Stephen J.; Waggoner, Stephen N.; Poirier, Steve; Olson, Steven H.; Marx, Steven O.; Van Doren, Steven R.; Sarilla, Suryakala; Brady-Kalnay, Susann M.; Dallman, Sydney; Azeem, Syeda Maryam; Teramoto, Tadahisa; Mehlman, Tamar; Swart, Tarryn; Abaffy, Tatjana; Akopian, Tatos; Haikarainen, Teemu; Moreda, Teresa Lozano; Ikegami, Tetsuro; Teixeira, Thaiz Rodrigues; Jayasinghe, Thilina D.; Gillingwater, Thomas H.; Kampourakis, Thomas; Richardson, Timothy I.; Herdendorf, Timothy J.; Kotzé, Timothy J.; O'Meara, Timothy R.; Corson, Timothy W.; Hermle, Tobias; Ogunwa, Tomisin Happy; Lan, Tong; Su, Tong; Banjo, Toshihiro; O'Mara, Tracy A.; Chou, Tristan; Chou, Tsui-Fen; Baumann, Ulrich; Desai, Umesh R.; Pai, Vaibhav P.; Thai, Van Chi; Tandon, Vasudha; Banerji, Versha; Robinson, Victoria L.; Gunasekharan, Vignesh; Namasivayam, Vigneshwaran; Segers, Vincent F. M.; Maranda, Vincent; Dolce, Vincenza; Maltarollo, Vinícius Gonçalves; Scoffone, Viola Camilla; Woods, Virgil A.; Ronchi, Virginia Paola; Van Hung Le, Vuong; Clayton, W. Brent; Lowther, W. Todd; Houry, Walid A.; Li, Wei; Tang, Weiping; Zhang, Wenjun; Van Voorhis, Wesley C.; Donaldson, William A.; Hahn, William C.; Kerr, William G.; Gerwick, William H.; Bradshaw, William J.; Foong, Wuen Ee; Blanchet, Xavier; Wu, Xiaoyang; Lu, Xin; Qi, Xin; Xu, Xin; Yu, Xinfang; Qin, Xingping; Wang, Xingyou; Yuan, Xinrui; Zhang, Xu; Zhang, Yan Jessie; Hu, Yanmei; Aldhamen, Yasser Ali; Chen, Yicheng; Li, Yihe; Sun, Ying; Zhu, Yini; Gupta, Yogesh K.; Pérez-Pertejo, Yolanda; Li, Yong; Tang, Young; He, Yuan; Tse-Dinh, Yuk-Ching; Sidorova, Yulia A.; Yen, Yun; Li, Yunlong; Frangos, Zachary J.; Chung, Zara; Su, Zhengchen; Wang, Zhenghe; Zhang, Zhiguo; Liu, Zhongle; Inde, Zintis; Artía, Zoraima; Heifets, Abraham
Contributors:	Null, Null; Wallach, Izhar; Bernard, Denzil; Nguyen, Kong; Ho, Gregory; Morrison, Adrian; Stecula, Adrian; Rosnik, Andreana; O'Sullivan, Ann Marie; Davtyan, Aram; Samudio, Ben; Thomas, Bill; Worley, Brad; Butler, Brittany; Laggner, Christian; Thayer, Desiree; Moharreri, Ehsan; Friedland, Greg; Truong, Ha; van den Bedem, Henry; Ng, Ho Leung; Stafford, Kate; Sarangapani, Krishna; Giesler, Kyle; Ngo, Lien; Mysinger, Michael; Ahmed, Mostafa; Anthis, Nicholas J.; Henriksen, Niel; Gniewek, Pawel; Eckert, Sam; de Oliveira, Saulo; Suterwala, Shabbir; Prasadprasad, Srimukh Veccham Krishna; Shek, Stefani; Contreras, Stephanie; Hare, Stephanie; Palazzo, Teresa; O'Brien, Terrence E.; Van Grack, Tessa; Williams, Tiffany; Chern, Ting-Rong; Kenyon, Victor; Lee, Andreia H.; Cann, Andrew B.; Bergman, Bastiaan; Anderson, Brandon M.; Cox, Bryan D.; Warrington, Jeffrey M.; Sorenson, Jon M.; Goldenberg, Joshua M.; Young, Matthew A.; Dehaan, Nichola; Pemberton, Ryan P.; Schroedl, Stefan; Abramyan, Tigran M.; Gupta, Tushita; Mysore, Venkatesh; Presser, Adam G.; Ferrando, Adolfo A.; Andricopulo, Adriano D.; Ghosh, Agnidipta; Ayachi, Aicha Gharbi; Mushtaq, Aisha; Shaqra, Ala M.; Toh, Alan Kie Leong; Smrcka, Alan V.; Ciccia, Alberto; de Oliveira, Aldo Sena; Sverzhinsky, Aleksandr; de Sousa, Alessandra Mara; Agoulnik, Alexander I.; Kushnir, Alexander; Freiberg, Alexander N.; Statsyuk, Alexander V.; Gingras, Alexandre R.; Degterev, Alexei; Tomilov, Alexey; Vrielink, Alice; Garaeva, Alisa A.; Bryant-Friedrich, Amanda; Caflisch, Amedeo; Patel, Amit K.; Rangarajan, Amith Vikram; Matheeussen, An; Battistoni, Andrea; Caporali, Andrea; Chini, Andrea; Ilari, Andrea; Mattevi, Andrea; Foote, Andrea Talbot; Trabocchi, Andrea; Stahl, Andrea; Herr, Andrew B.; Berti, Andrew; Freywald, Andrew; Reidenbach, Andrew G.; Lam, Andrew; Cuddihy, Andrew R.; White, Andrew
Publisher Information:	NATURE PORTFOLIO; HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
Publication Year:	2024
Collection:	Sapienza Università di Roma: CINECA IRIS
Subject Terms:	computational drug discovery; virtual screening; protein target; structure-based drug discovery
Description:	High throughput screening ( HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet((R)) convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet((R)) model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery.
Document Type:	article in journal/newspaper
Language:	English
Relation:	info:eu-repo/semantics/altIdentifier/pmid/38565852; info:eu-repo/semantics/altIdentifier/wos/WOS:001253148000001; volume:14; issue:1; firstpage:1; lastpage:16; numberofpages:16; journal:SCIENTIFIC REPORTS; https://hdl.handle.net/11573/1719535
DOI:	10.1038/s41598-024-54655-z
Availability:	https://hdl.handle.net/11573/1719535; https://doi.org/10.1038/s41598-024-54655-z
Rights:	info:eu-repo/semantics/openAccess
Accession Number:	edsbas.C26DF005
Database:	BASE