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Publications

2026

  • Autopalmitoylation of IDH1-R132H regulates its neomorphic activity in cancer cells
    L Hu, J Lin, L Sun, AM Berezuk, KS Tuttle, X Zhu, HS Seo, S Dhe-Paganon, P Li, Y Sun, L Ni, J Zhang, D Tan, H Wakimoto, DP Cahill, X Bai, X Luo, JM Asara, S Subramaniam, Y Shan, X Wu
    Nature Chemical Biology.
    DOI / Article

2025

  • Trillion Ligands per Day: Performance-Portable Virtual Screening via Compound Database Optimization and Multi-Target Docking
    X Duan, C Shen, G Chen, S Wu, Y Wang, Y Chen, Q Chang, Q Xia, Z Yin, L Gan, Y Shan, G Yang, W Liu, N Huang
    SC '25: The International Conference for High Performance Computing, Networking, Storage and Analysis.
    DOI / Article   |   Cited by 2

2024

  • BCR::ABL1 kinase N-lobe mutants confer moderate to high degrees of resistance to asciminib
    A Leyte-Vidal, DG Ruiz, R DeFilippis, IB Leske, D Rea, S Phan, KB Miller, F Hu, A Mase, Y Shan, O Hantschel, MP Jacobson, NP Shah
    Blood 144(6):639-645.
    DOI / Article   |   Cited by 35
  • Discovering Modulators of KRAS Nanoclustering
    JN Kapp, MJV Liste, G Nagy-Davidescu, S van Ruitenbeck, M Loza, J Brea, Y Shan, A Plückthun
    Mechanisms of Ras Oncogene Inhibition, 210.
  • Experimental variables determine the outcome of RAS-RAS interactions
    Z Zhou, TL Nguyen, X Li, C Poujol, E Berlinska, SV Michelina, JN Kapp, A Plückthun, MM Winslow, C Ambrogio, Y Shan, D Santamaría, KD Westover
    Journal of Biological Chemistry 300(11):107859.
    DOI / Article   |   Cited by 8

2023

  • Structural mechanism of a drug-binding process involving a large conformational change of the protein target
    P Ayaz, A Lyczek, Y Paung, VR Mingione, RE Iacob, PWd Waal, JR Engen, MA Seeliger, Y Shan, DE Shaw
    Nature Communications 14(1):1885.
    DOI / Article   |   Cited by 103

2022

  • How does a small molecule bind at a cryptic binding site?
    Y Shan, VP Mysore, AE Leffler, ET Kim, S Sagawa, DE Shaw
    PLOS Computational Biology 18(3):e1009817.
    DOI / Article   |   Cited by 52
  • Targetable HER3 functions driving tumorigenic signaling in HER2-amplified cancers
    MR Campbell, A Ruiz-Saenz, E Peterson, C Agnew, P Ayaz, S Garfinkle, P Littlefield, V Steri, J Oeffinger, M Sampang, Y Shan, DE Shaw, N Jura, MM Moasser
    Cell Reports 38(5):110291.
    DOI / Article   |   Cited by 20
  • Validation of an allosteric binding site of Src kinase identified by unbiased ligand binding simulations
    VR Mingione, ZH Foda, Y Paung, H Philipose, AM Rangwala, Y Shan, MA Seeliger
    Journal of molecular biology 434 (17), 167628.
    DOI / Article   |   Cited by 13

2021

  • A putative structural mechanism underlying the antithetic effect of homologous RND1 and RhoD GTPases in mammalian plexin regulation
    Y Liu, P Ke, YC Kuo, Y Wang, X Zhang, C Song, Y Shan
    eLife 10:e64304.
    DOI / Article   |   Cited by 10
  • A structural model of a Ras–Raf signalosome
    VP Mysore, ZW Zhou, C Ambrogio, L Li, JN Kapp, C Lu, Q Wang, MR Tucker, JJ Okoro, G Nagy-Davidescu, X Bai, A Plückthun, PA Jänne, KD Westover, Y Shan, DE Shaw
    Nature Structural & Molecular Biology 28(10):847-857.
    DOI / Article   |   Cited by 81
  • Structural basis for ALK2/BMPR2 receptor complex signaling through kinase domain oligomerization
    C Agnew, P Ayaz, R Kashima, HS Loving, P Ghatpande, JE Kung, ES Underbakke, Y Shan, DE Shaw, A Hata, N Jura
    Nature Communications 12(1):4950.
    DOI / Article   |   Cited by 51

2020

  • Structural basis of AZD9291 selectivity for EGFR T790M
    XE Yan, P Ayaz, SJ Zhu, P Zhao, L Liang, CH Zhang, YC Wu, JL Li, HG Choi, X Huang, Y Shan, DE Shaw, CH Yun
    Journal of medicinal chemistry 63 (15), 8502-8511.
    DOI / Article   |   Cited by 117

2019

  • Structural models of full-length JAK2 kinase
    P Ayaz, HM Hammarén, J Raivola, D Sharon, SR Hubbard, O Silvennoinen, Y Shan, DE Shaw
    bioRxiv, 727727.
    DOI / Article   |   Cited by 8

2018

  • The architecture of EGFR's basal complexes reveals autoinhibition mechanisms in dimers and oligomers
    LC Zanetti-Domingues, D Korovesis, SR Needham, CJ Tynan, S Sagawa, A Arkhipov, VP Mysore, SK Roberts, ET Kim, V Losasso, DJ Clarke, M Hirsch, ML Martin-Fernandez, DT Clarke, AHA Clayton, M Perani, LJ Pike, PJ Parker, Y Shan, DE Shaw
    Nature communications 9 (1), 4325.
    DOI / Article   |   Cited by 96

2016

  • EGFR oligomerization organizes kinase-active dimers into competent signalling platforms
    SR Needham, SK Roberts, A Arkhipov, VP Mysore, CJ Tynan, LC Zanetti-Domingues, ET Kim, V Losasso, D Korovesis, M Hirsch, DJ Rolfe, DT Clarke, MD Winn, A Lajevardipour, AHA Clayton, LJ Pike, M Perani, PJ Parker, Y Shan, DE Shaw, ML Martin-Fernandez
    Nature Communications 7:13307.
    DOI / Article   |   Cited by 216

2015

  • A dynamically coupled allosteric network underlies binding cooperativity in Src kinase
    ZH Foda, Y Shan, ET Kim, DE Shaw, MA Seeliger
    Nature communications 6 (1), 5939.
    DOI / Article   |   Cited by 141
  • Allosteric activation of apicomplexan calcium-dependent protein kinases
    JR Ingram, KE Knockenhauer, BM Markus, J Mandelbaum, A Ramek, Y Shan, DE Shaw, TU Schwartz, HL Ploegh, S Lourido
    Proceedings of the National Academy of Sciences 112 (36), E4975-E4984.
    DOI / Article   |   Cited by 66

2014

  • Assessing the accuracy of two enhanced sampling methods using EGFR kinase transition pathways: the influence of collective variable choice
    AC Pan, TM Weinreich, Y Shan, DP Scarpazza, DE Shaw
    Journal of Chemical Theory and Computation 10 (7), 2860-2865.
    DOI / Article   |   Cited by 41
  • How IGF-1 activates its receptor
    JM Kavran, JM McCabe, PO Byrne, MK Connacher, Z Wang, A Ramek, S Sarabipour, Y Shan, DE Shaw, K Hristova, PA Cole, DJ Leahy
    Elife 3, e03772.
    DOI / Article   |   Cited by 244
  • IRAK4 dimerization and trans-autophosphorylation are induced by Myddosome assembly
    R Ferrao, H Zhou, Y Shan, Q Liu, Q Li, DE Shaw, X Li, H Wu
    Molecular cell 55 (6), 891-903.
    DOI / Article   |   Cited by 175
  • Membrane interaction of bound ligands contributes to the negative binding cooperativity of the EGF receptor
    A Arkhipov, Y Shan, ET Kim, DE Shaw
    PLoS computational biology 10 (7), e1003742.
    DOI / Article   |   Cited by 50
  • Molecular basis for pseudokinase-dependent autoinhibition of JAK2 tyrosine kinase
    Y Shan, K Gnanasambandan, D Ungureanu, ET Kim, H Hammarén, K Yamashita, O Silvennoinen, DE Shaw, SR Hubbard
    Nature structural & molecular biology 21 (7), 579-584.
    DOI / Article   |   Cited by 187
  • Structural analysis of the EGFR/HER3 heterodimer reveals the molecular basis for activating HER3 mutations
    P Littlefield, L Liu, V Mysore, Y Shan, DE Shaw, N Jura
    Science signaling 7 (354), ra114-ra114.
    DOI / Article   |   Cited by 149

2013

  • Architecture and membrane interactions of the EGF receptor
    A Arkhipov, Y Shan, R Das, NF Endres, MP Eastwood, DE Wemmer, J Kuriyan, DE Shaw
    Cell 152 (3), 557-569.
    DOI / Article   |   Cited by 610
  • Conformational coupling across the plasma membrane in activation of the EGF receptor
    NF Endres, R Das, AW Smith, A Arkhipov, E Kovacs, Y Huang, JG Pelton, Y Shan, DE Shaw, DE Wemmer, JT Groves, J Kuriyan
    Cell 152 (3), 543-556.
    DOI / Article   |   Cited by 584
  • Her2 activation mechanism reflects evolutionary preservation of asymmetric ectodomain dimers in the human EGFR family
    A Arkhipov, Y Shan, ET Kim, RO Dror, DE Shaw
    Elife 2, e00708.
    DOI / Article   |   Cited by 101
  • Transitions to catalytically inactive conformations in EGFR kinase
    Y Shan, A Arkhipov, ET Kim, AC Pan, DE Shaw
    Proceedings of the National Academy of Sciences 110 (18), 7270-7275.
    DOI / Article   |   Cited by 241

2012

  • Crystal structures of the JAK2 pseudokinase domain and the pathogenic mutant V617F
    RM Bandaranayake, D Ungureanu, Y Shan, DE Shaw, O Silvennoinen, SR Hubbard
    Nature structural & molecular biology 19 (8), 754-759.
    DOI / Article   |   Cited by 305
  • Oncogenic mutations counteract intrinsic disorder in the EGFR kinase and promote receptor dimerization
    Y Shan, MP Eastwood, X Zhang, ET Kim, A Arkhipov, RO Dror, J Jumper, J Kuriyan, DE Shaw
    Cell 149 (4), 860-870.
    DOI / Article   |   Cited by 456
  • Regulation of RAS oncogenicity by acetylation
    MH Yang, S Nickerson, ET Kim, C Liot, G Laurent, R Spang, MR Philips, Y Shan, DE Shaw, D Bar-Sagi, MC Haigis, KM Haigis
    Proceedings of the National Academy of Sciences 109 (27), 10843-10848.
    DOI / Article   |   Cited by 154

2011

  • How does a drug molecule find its target binding site?
    Y Shan, ET Kim, MP Eastwood, RO Dror, MA Seeliger, DE Shaw
    Journal of the American Chemical Society 133 (24), 9181-9183.
    DOI / Article   |   Cited by 747
  • Pathway and mechanism of drug binding to G-protein-coupled receptors
    RO Dror, AC Pan, DH Arlow, DW Borhani, P Maragakis, Y Shan, H Xu, DE Shaw
    Proceedings of the National Academy of Sciences 108 (32), 13118-13123.
    DOI / Article   |   Cited by 893

2010

  • Atomic-level characterization of the structural dynamics of proteins
    DE Shaw, P Maragakis, K Lindorff-Larsen, S Piana, RO Dror, MP Eastwood, JA Bank, JM Jumper, JK Salmon, Y Shan, W Wriggers
    Science 330 (6002), 341-346.
    DOI / Article   |   Cited by 2335

2009

  • A conserved protonation-dependent switch controls drug binding in the Abl kinase
    Y Shan, MA Seeliger, MP Eastwood, F Frank, H Xu, MØ Jensen, RO Dror, J Kuriyan, DE Shaw
    Proceedings of the National Academy of Sciences 106 (1), 139-144.
    DOI / Article   |   Cited by 319
  • Automated event detection and activity monitoring in long molecular dynamics simulations
    W Wriggers, KA Stafford, Y Shan, S Piana, P Maragakis, K Lindorff-Larsen, PJ Miller, J Gullingsrud, CA Rendleman, MP Eastwood, RO Dror, DE Shaw
    Journal of chemical theory and computation 5 (10), 2595-2605.
    DOI / Article   |   Cited by 61
  • Equally potent inhibition of c-Src and Abl by compounds that recognize inactive kinase conformations
    MA Seeliger, P Ranjitkar, C Kasap, Y Shan, DE Shaw, NP Shah, J Kuriyan, DJ Maly
    Cancer research 69 (6), 2384-2392.
    DOI / Article   |   Cited by 190
  • Millisecond-scale molecular dynamics simulations on Anton
    DE Shaw, RO Dror, JK Salmon, JP Grossman, KM Mackenzie, JA Bank, C Young, MM Deneroff, B Batson, KJ Bowers, E Chow, MP Eastwood, D Ierardi, JL Klepeis, J Kuskin, RH Larson, K Lindorff-Larsen, P Maragakis, MA Moraes, S Piana, Y Shan, B Towles
    Proceedings of the Conference on High Performance Computing, Networking, Storage and Analysis.
    DOI / Article   |   Cited by 740
  • Structural analysis of the catalytically inactive kinase domain of the human EGF receptor 3
    N Jura, Y Shan, X Cao, DE Shaw, J Kuriyan
    Proceedings of the National Academy of Sciences 106 (51), 21608-21613.
    DOI / Article   |   Cited by 410

2008

  • Anton, a special-purpose machine for molecular dynamics simulation
    DE Shaw, MM Deneroff, RO Dror, JS Kuskin, RH Larson, JK Salmon, C Young, B Batson, KJ Bowers, JC Chao, MP Eastwood, J Gagliardo, JP Grossman, CR Ho, DJ Ierardi, I Kolossvary, JL Klepeis, T Layman, C McLeavey, MA Moraes, R Mueller, EC Priest, Y Shan, J Spengler, M Theobald, B Towles, SC Wang
    Communications of the ACM 51 (7), 91-97.
    DOI / Article   |   Cited by 1053
  • High-throughput pairwise point interactions in Anton, a specialized machine for molecular dynamics simulation
    RH Larson, JK Salmon, RO Dror, MM Deneroff, C Young, JP Grossman, Y Shan, JL Klepeis, DE Shaw
    2008 IEEE 14th International Symposium on High-Performance Computer Architecture.
    DOI / Article   |   Cited by 40

2007

  • Anton, a special-purpose machine for molecular dynamics simulation
    DE Shaw, MM Deneroff, RO Dror, JS Kuskin, RH Larson, JK Salmon, C Young, B Batson, KJ Bowers, JC Chao, MP Eastwood, J Gagliardo, JP Grossman, CR Ho, DJ Ierardi, I Kolossvary, JL Klepeis, T Layman, C McLeavey, MA Moraes, R Mueller, EC Priest, Y Shan, J Spengler, M Theobald, B Towles, SC Wang
    ACM SIGARCH Computer Architecture News 35 (2), 1-12.
    DOI / Article   |   Cited by 378
  • Mechanism of Na+/H+ antiporting
    IT Arkin, H Xu, MO Jensen, E Arbely, ER Bennett, KJ Bowers, E Chow, RO Dror, MP Eastwood, R Flitman-Tene, BA Gregersen, JL Klepeis, I Kolossvary, Y Shan, DE Shaw
    Science 317 (5839), 799-803.
    Cited by 184

2006

  • Scalable algorithms for molecular dynamics simulations on commodity clusters
    KJ Bowers, E Chow, H Xu, RO Dror, MP Eastwood, BA Gregersen, JL Klepeis, I Kolossvary, MA Moraes, FD Sacerdoti, JK Salmon, Y Shan, DE Shaw
    Proceedings of the 2006 ACM/IEEE Conference on Supercomputing, 84-es.
    DOI / Article   |   Cited by 4427

2005

  • Gaussian split Ewald: A fast Ewald mesh method for molecular simulation
    Y Shan, JL Klepeis, MP Eastwood, RO Dror, DE Shaw
    The Journal of chemical physics 122 (5), 054101.
    DOI / Article   |   Cited by 471

2001

  • Fold recognition and accurate query‐template alignment by a combination of PSI‐BLAST and threading
    Y Shan, G Wang, HX Zhou
    Proteins: Structure, Function, and Bioinformatics 42 (1), 23-37.
    DOI / Article   |   Cited by 47
  • Prediction of protein interaction sites from sequence profile and residue neighbor list
    HX Zhou, Y Shan
    Proteins: Structure, Function, and Bioinformatics 44 (3), 336-343.
    DOI / Article   |   Cited by 406

2000

  • Correspondence of potentials of mean force in proteins and in liquids
    Y Shan, HX Zhou
    The Journal of Chemical Physics 113 (11), 4794-4798.
    DOI / Article   |   Cited by 5