5rug › Citations

Fragment binding to the Nsp3 macrodomain of SARS-CoV-2 identified through crystallographic screening and computational docking.

<div class='caption-title'>Overview of the fragment discovery approach for SARS-CoV-2 Nsp3 Mac1 presented in this study.</div>
<div class='caption-title'>Crystallographic screening identified 234 fragments bound to Mac1.</div>
<div class='caption-title'>Docking hits confirmed by high-resolution crystal structures.</div>
Schuller M, Correy GJ, Gahbauer S, Fearon D, Wu T, Díaz RE, Young ID, Carvalho Martins L, Smith DH, Schulze-Gahmen U, Owens TW, Deshpande I, Merz GE, Thwin AC, Biel JT, Peters JK, Moritz M, Herrera N, Kratochvil HT, Aimon A, Bennett JM, Brandao Neto J, Cohen AE, Dias A, Douangamath A, Dunnett L, Fedorov O, Ferla MP, Fuchs MR, Gorrie-Stone TJ, Holton JM, Johnson MG, Krojer T, Meigs G, Powell AJ, Rack JGM, Rangel VL, Russi S, Skyner RE, Smith CA, Soares AS, Wierman JL, Zhu K, O'Brien P, Jura N, Ashworth A, Irwin JJ, Thompson MC, Gestwicki JE, von Delft F, Shoichet BK, Fraser JS, Ahel I
OpenAccess logo Sci Adv 7 (2021)
Related entries: 5rs7, 5rs8, 5rs9, 5rsb, 5rsc, 5rsd, 5rse, 5rsf, 5rsg, 5rsh, 5rsi, 5rsj, 5rsk, 5rsl, 5rsm, 5rsn, 5rso, 5rsp, 5rsq, 5rsr, 5rss, 5rst, 5rsu, 5rsv, 5rsw, 5rsx, 5rsy, 5rsz, 5rt0, 5rt1, 5rt2, 5rt3, 5rt4, 5rt5, 5rt6, 5rt7, 5rt8, 5rt9, 5rta, 5rtb, 5rtc, 5rtd, 5rte, 5rtf, 5rtg, 5rth, 5rti, 5rtj, 5rtk, 5rtl, 5rtm, 5rtn, 5rto, 5rtp, 5rtq, 5rtr, 5rts, 5rtt, 5rtu, 5rtv, 5rtw, 5rtx, 5rty, 5rtz, 5ru0, 5ru1, 5ru2, 5ru3, 5ru4, 5ru5, 5ru6, 5ru7, 5ru8, 5ru9, 5rua, 5ruc, 5rud, 5rue, 5ruf, 5ruh, 5rui, 5ruj, 5ruk, 5rul, 5rum, 5run, 5ruo, 5rup, 5ruq, 5rur, 5rus, 5rut, 5ruu, 5ruv, 5ruw, 5rux, 5ruy, 5ruz, 5rv0, 5rv1, 5rv2, 5rv3, 5rv4, 5rv5, 5rv6, 5rv7, 5rv8, 5rv9, 5rva, 5rvb, 5rvc, 5rvd, 5rve, 5rvf, 5rvg, 5rvh, 5rvi, 5rvj, 5rvk, 5rvl, 5rvm, 5rvn, 5rvo, 5rvp, 5rvq, 5rvr, 5rvs, 5rvt, 5rvu, 5rvv, 5s18, 5s1a, 5s1c, 5s1e, 5s1g, 5s1i, 5s1k, 5s1m, 5s1o, 5s1q, 5s1s, 5s1u, 5s1w, 5s1y, 5s20, 5s22, 5s24, 5s26, 5s27, 5s28, 5s29, 5s2a, 5s2b, 5s2c, 5s2d, 5s2e, 5s2f, 5s2g, 5s2h, 5s2i, 5s2j, 5s2k, 5s2l, 5s2m, 5s2n, 5s2o, 5s2p, 5s2q, 5s2r, 5s2s, 5s2t, 5s2u, 5s2v, 5s2w, 5s2x, 5s2y, 5s2z, 5s30, 5s31, 5s32, 5s33, 5s34, 5s35, 5s36, 5s37, 5s38, 5s39, 5s3a, 5s3b, 5s3c, 5s3d, 5s3e, 5s3f, 5s3g, 5s3h, 5s3i, 5s3j, 5s3k, 5s3l, 5s3m, 5s3n, 5s3o, 5s3p, 5s3q, 5s3r, 5s3s, 5s3t, 5s3u, 5s3v, 5s3w, 5s3x, 5s3y, 5s3z, 5s40, 5s41, 5s42, 5s43, 5s44, 5s45, 5s46, 5s47, 5s48, 5s49, 5s4a, 5s4b, 5s4c, 5s4d, 5s4e, 5s4f, 5s4g, 5s4h, 5s4i, 5s4j, 5s4k, 7kqo, 7kqp, 7kqw, 7kr0, 7kr1

Cited: 67 times
EuropePMC logo PMID: 33853786

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) macrodomain within the nonstructural protein 3 counteracts host-mediated antiviral adenosine diphosphate-ribosylation signaling. This enzyme is a promising antiviral target because catalytic mutations render viruses nonpathogenic. Here, we report a massive crystallographic screening and computational docking effort, identifying new chemical matter primarily targeting the active site of the macrodomain. Crystallographic screening of 2533 diverse fragments resulted in 214 unique macrodomain-binders. An additional 60 molecules were selected from docking more than 20 million fragments, of which 20 were crystallographically confirmed. X-ray data collection to ultra-high resolution and at physiological temperature enabled assessment of the conformational heterogeneity around the active site. Several fragment hits were confirmed by solution binding using three biophysical techniques (differential scanning fluorimetry, homogeneous time-resolved fluorescence, and isothermal titration calorimetry). The 234 fragment structures explore a wide range of chemotypes and provide starting points for development of potent SARS-CoV-2 macrodomain inhibitors.

Articles - 5rug mentioned but not cited (1)

  1. research-article Fragment Binding to the Nsp3 Macrodomain of SARS-CoV-2 Identified Through Crystallographic Screening and Computational Docking. Schuller M, Correy GJ, Gahbauer S, Fearon D, Wu T, Díaz RE, Young ID, Martins LC, Smith DH, Schulze-Gahmen U, Owens TW, Deshpande I, Merz GE, Thwin AC, Biel JT, Peters JK, Moritz M, Herrera N, Kratochvil HT, QCRG Structural Biology Consortium, Aimon A, Bennett JM, Neto JB, Cohen AE, Dias A, Douangamath A, Dunnett L, Fedorov O, Ferla MP, Fuchs M, Gorrie-Stone TJ, Holton JM, Johnson MG, Krojer T, Meigs G, Powell AJ, Johannes Gregor Matthias Rack, Rangel VL, Russi S, Skyner RE, Smith CA, Soares AS, Wierman JL, Zhu K, Jura N, Ashworth A, Irwin J, Thompson MC, Gestwicki JE, von Delft F, Shoichet BK, Fraser JS, Ahel I. bioRxiv 2020.11.24.393405 (2020)


Reviews citing this publication (16)

  1. A practical guide to large-scale docking. Bender BJ, Gahbauer S, Luttens A, Lyu J, Webb CM, Stein RM, Fink EA, Balius TE, Carlsson J, Irwin JJ, Shoichet BK. Nat Protoc 16 4799-4832 (2021)
  2. Structural biology of SARS-CoV-2: open the door for novel therapies. Yan W, Zheng Y, Zeng X, He B, Cheng W. Signal Transduct Target Ther 7 26 (2022)
  3. Computational approaches streamlining drug discovery. Sadybekov AV, Katritch V. Nature 616 673-685 (2023)
  4. ADP-ribosylation systems in bacteria and viruses. Mikolčević P, Hloušek-Kasun A, Ahel I, Mikoč A. Comput Struct Biotechnol J 19 2366-2383 (2021)
  5. Accelerating antiviral drug discovery: lessons from COVID-19. von Delft A, Hall MD, Kwong AD, Purcell LA, Saikatendu KS, Schmitz U, Tallarico JA, Lee AA. Nat Rev Drug Discov 22 585-603 (2023)
  6. Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2. Gao K, Wang R, Chen J, Cheng L, Frishcosy J, Huzumi Y, Qiu Y, Schluckbier T, Wei X, Wei GW. Chem Rev 122 11287-11368 (2022)
  7. Host ADP-ribosylation and the SARS-CoV-2 macrodomain. Hoch NC. Biochem Soc Trans 49 1711-1721 (2021)
  8. Advances in Pathogenesis, Progression, Potential Targets and Targeted Therapeutic Strategies in SARS-CoV-2-Induced COVID-19. Zhou H, Ni WJ, Huang W, Wang Z, Cai M, Sun YC. Front Immunol 13 834942 (2022)
  9. Intracellular mono-ADP-ribosyltransferases at the host-virus interphase. Lüscher B, Verheirstraeten M, Krieg S, Korn P. Cell Mol Life Sci 79 288 (2022)
  10. NAD+ Degrading Enzymes, Evidence for Roles During Infection. Tan A, Doig CL. Front Mol Biosci 8 697359 (2021)
  11. An Update on the Current State of SARS-CoV-2 Mac1 Inhibitors. O'Connor JJ, Ferraris D, Fehr AR. Pathogens 12 1221 (2023)
  12. Improved understanding of biorisk for research involving microbial modification using annotated sequences of concern. Godbold GD, Hewitt FC, Kappell AD, Scholz MB, Agar SL, Treangen TJ, Ternus KL, Sandbrink JB, Koblentz GD. Front Bioeng Biotechnol 11 1124100 (2023)
  13. PARPs and ADP-Ribosylation in Chronic Inflammation: A Focus on Macrophages. Santinelli-Pestana DV, Aikawa E, Singh SA, Aikawa M. Pathogens 12 964 (2023)
  14. Medicinal chemistry strategies towards the development of non-covalent SARS-CoV-2 Mpro inhibitors. Song L, Gao S, Ye B, Yang M, Cheng Y, Kang D, Yi F, Sun JP, Menéndez-Arias L, Neyts J, Liu X, Zhan P. Acta Pharm Sin B 14 87-109 (2024)
  15. Targeting SARS-CoV-2 nonstructural protein 3: Function, structure, inhibition, and perspective in drug discovery. Li X, Song Y. Drug Discov Today 29 103832 (2024)
  16. The Potential Protective Role of GS-441524, a Metabolite of the Prodrug Remdesivir, in Vaccine Breakthrough SARS-CoV-2 Infections. Zhu J, Li Y, Liang J, Mubareka S, Slutsky AS, Zhang H. Intensive Care Res 2 49-60 (2022)

Articles citing this publication (50)

  1. Structure, mechanism and crystallographic fragment screening of the SARS-CoV-2 NSP13 helicase. Newman JA, Douangamath A, Yadzani S, Yosaatmadja Y, Aimon A, Brandão-Neto J, Dunnett L, Gorrie-Stone T, Skyner R, Fearon D, Schapira M, von Delft F, Gileadi O. Nat Commun 12 4848 (2021)
  2. Ultralarge Virtual Screening Identifies SARS-CoV-2 Main Protease Inhibitors with Broad-Spectrum Activity against Coronaviruses. Luttens A, Gullberg H, Abdurakhmanov E, Vo DD, Akaberi D, Talibov VO, Nekhotiaeva N, Vangeel L, De Jonghe S, Jochmans D, Krambrich J, Tas A, Lundgren B, Gravenfors Y, Craig AJ, Atilaw Y, Sandström A, Moodie LWK, Lundkvist Å, van Hemert MJ, Neyts J, Lennerstrand J, Kihlberg J, Sandberg K, Danielson UH, Carlsson J. J Am Chem Soc 144 2905-2920 (2022)
  3. Structures of the σ2 receptor enable docking for bioactive ligand discovery. Alon A, Lyu J, Braz JM, Tummino TA, Craik V, O'Meara MJ, Webb CM, Radchenko DS, Moroz YS, Huang XP, Liu Y, Roth BL, Irwin JJ, Basbaum AI, Shoichet BK, Kruse AC. Nature 600 759-764 (2021)
  4. The SARS-CoV-2 Nsp3 macrodomain reverses PARP9/DTX3L-dependent ADP-ribosylation induced by interferon signaling. Russo LC, Tomasin R, Matos IA, Manucci AC, Sowa ST, Dale K, Caldecott KW, Lehtiö L, Schechtman D, Meotti FC, Bruni-Cardoso A, Hoch NC. J Biol Chem 297 101041 (2021)
  5. Structure-based discovery of nonopioid analgesics acting through the α2A-adrenergic receptor. Fink EA, Xu J, Hübner H, Braz JM, Seemann P, Avet C, Craik V, Weikert D, Schmidt MF, Webb CM, Tolmachova NA, Moroz YS, Huang XP, Kalyanaraman C, Gahbauer S, Chen G, Liu Z, Jacobson MP, Irwin JJ, Bouvier M, Du Y, Shoichet BK, Basbaum AI, Gmeiner P. Science 377 eabn7065 (2022)
  6. Disulfide Bonds Play a Critical Role in the Structure and Function of the Receptor-binding Domain of the SARS-CoV-2 Spike Antigen. Grishin AM, Dolgova NV, Landreth S, Fisette O, Pickering IJ, George GN, Falzarano D, Cygler M. J Mol Biol 434 167357 (2022)
  7. Iterative computational design and crystallographic screening identifies potent inhibitors targeting the Nsp3 macrodomain of SARS-CoV-2. Gahbauer S, Correy GJ, Schuller M, Ferla MP, Doruk YU, Rachman M, Wu T, Diolaiti M, Wang S, Neitz RJ, Fearon D, Radchenko DS, Moroz YS, Irwin JJ, Renslo AR, Taylor JC, Gestwicki JE, von Delft F, Ashworth A, Ahel I, Shoichet BK, Fraser JS. Proc Natl Acad Sci U S A 120 e2212931120 (2023)
  8. Letter High-Throughput Activity Assay for Screening Inhibitors of the SARS-CoV-2 Mac1 Macrodomain. Dasovich M, Zhuo J, Goodman JA, Thomas A, McPherson RL, Jayabalan AK, Busa VF, Cheng SJ, Murphy BA, Redinger KR, Alhammad YMO, Fehr AR, Tsukamoto T, Slusher BS, Bosch J, Wei H, Leung AKL. ACS Chem Biol 17 17-23 (2022)
  9. A molecular toolbox for ADP-ribosyl binding proteins. Sowa ST, Galera-Prat A, Wazir S, Alanen HI, Maksimainen MM, Lehtiö L. Cell Rep Methods 1 100121 (2021)
  10. Structural Insights into Plasticity and Discovery of Remdesivir Metabolite GS-441524 Binding in SARS-CoV-2 Macrodomain. Ni X, Schröder M, Olieric V, Sharpe ME, Hernandez-Olmos V, Proschak E, Merk D, Knapp S, Chaikuad A. ACS Med Chem Lett 12 603-609 (2021)
  11. The mechanisms of catalysis and ligand binding for the SARS-CoV-2 NSP3 macrodomain from neutron and x-ray diffraction at room temperature. Correy GJ, Kneller DW, Phillips G, Pant S, Russi S, Cohen AE, Meigs G, Holton JM, Gahbauer S, Thompson MC, Ashworth A, Coates L, Kovalevsky A, Meilleur F, Fraser JS. Sci Adv 8 eabo5083 (2022)
  12. Exploring protein hotspots by optimized fragment pharmacophores. Bajusz D, Wade WS, Satała G, Bojarski AJ, Ilaš J, Ebner J, Grebien F, Papp H, Jakab F, Douangamath A, Fearon D, von Delft F, Schuller M, Ahel I, Wakefield A, Vajda S, Gerencsér J, Pallai P, Keserű GM. Nat Commun 12 3201 (2021)
  13. Modeling the expansion of virtual screening libraries. Lyu J, Irwin JJ, Shoichet BK. Nat Chem Biol 19 712-718 (2023)
  14. Unique Mutations in the Murine Hepatitis Virus Macrodomain Differentially Attenuate Virus Replication, Indicating Multiple Roles for the Macrodomain in Coronavirus Replication. Voth LS, O'Connor JJ, Kerr CM, Doerger E, Schwarting N, Sperstad P, Johnson DK, Fehr AR. J Virol 95 e0076621 (2021)
  15. Discovery of compounds that inhibit SARS-CoV-2 Mac1-ADP-ribose binding by high-throughput screening. Roy A, Alhammad YM, McDonald P, Johnson DK, Zhuo J, Wazir S, Ferraris D, Lehtiö L, Leung AKL, Fehr AR. Antiviral Res 203 105344 (2022)
  16. The Conserved Macrodomain Is a Potential Therapeutic Target for Coronaviruses and Alphaviruses. Leung AKL, Griffin DE, Bosch J, Fehr AR. Pathogens 11 94 (2022)
  17. SARS-CoV-2 Mac1 is required for IFN antagonism and efficient virus replication in cell culture and in mice. Alhammad YM, Parthasarathy S, Ghimire R, Kerr CM, O'Connor JJ, Pfannenstiel JJ, Chanda D, Miller CA, Baumlin N, Salathe M, Unckless RL, Zuñiga S, Enjuanes L, More S, Channappanavar R, Fehr AR. Proc Natl Acad Sci U S A 120 e2302083120 (2023)
  18. Combining High-Throughput Synthesis and High-Throughput Protein Crystallography for Accelerated Hit Identification. Sutanto F, Shaabani S, Oerlemans R, Eris D, Patil P, Hadian M, Wang M, Sharpe ME, Groves MR, Dömling A. Angew Chem Int Ed Engl 60 18231-18239 (2021)
  19. Design, synthesis and evaluation of inhibitors of the SARS-CoV-2 nsp3 macrodomain. Sherrill LM, Joya EE, Walker A, Roy A, Alhammad YM, Atobatele M, Wazir S, Abbas G, Keane P, Zhuo J, Leung AKL, Johnson DK, Lehtiö L, Fehr AR, Ferraris D. Bioorg Med Chem 67 116788 (2022)
  20. Room-temperature crystallography reveals altered binding of small-molecule fragments to PTP1B. Skaist Mehlman T, Biel JT, Azeem SM, Nelson ER, Hossain S, Dunnett L, Paterson NG, Douangamath A, Talon R, Axford D, Orins H, von Delft F, Keedy DA. Elife 12 e84632 (2023)
  21. Simplified quality assessment for small-molecule ligands in the Protein Data Bank. Shao C, Westbrook JD, Lu C, Bhikadiya C, Peisach E, Young JY, Duarte JM, Lowe R, Wang S, Rose Y, Feng Z, Burley SK. Structure 30 252-262.e4 (2022)
  22. Venus: Elucidating the Impact of Amino Acid Variants on Protein Function Beyond Structure Destabilisation. Ferla MP, Pagnamenta AT, Koukouflis L, Taylor JC, Marsden BD. J Mol Biol 434 167567 (2022)
  23. Natural Apocarotenoids and Their Synthetic Glycopeptide Conjugates Inhibit SARS-CoV-2 Replication. Bereczki I, Papp H, Kuczmog A, Madai M, Nagy V, Agócs A, Batta G, Milánkovits M, Ostorházi E, Mitrović A, Kos J, Zsigmond Á, Hajdú I, Lőrincz Z, Bajusz D, Keserű GM, Hodek J, Weber J, Jakab F, Herczegh P, Borbás A. Pharmaceuticals (Basel) 14 1111 (2021)
  24. Large library docking for novel SARS-CoV-2 main protease non-covalent and covalent inhibitors. Fink EA, Bardine C, Gahbauer S, Singh I, Detomasi TC, White K, Gu S, Wan X, Chen J, Ary B, Glenn I, O'Connell J, O'Donnell H, Fajtová P, Lyu J, Vigneron S, Young NJ, Kondratov IS, Alisoltani A, Simons LM, Lorenzo-Redondo R, Ozer EA, Hultquist JF, O'Donoghue AJ, Moroz YS, Taunton J, Renslo AR, Irwin JJ, García-Sastre A, Shoichet BK, Craik CS. Protein Sci 32 e4712 (2023)
  25. Creating collaboration by breaking down scientific barriers. Fabius JM, Krogan NJ. Cell 184 2271-2275 (2021)
  26. Current status of structure-based drug repurposing against COVID-19 by targeting SARS-CoV-2 proteins. Hijikata A, Shionyu C, Nakae S, Shionyu M, Ota M, Kanaya S, Shirai T. Biophys Physicobiol 18 226-240 (2021)
  27. PARP14 is a writer, reader, and eraser of mono-ADP-ribosylation. Torretta A, Chatzicharalampous C, Ebenwaldner C, Schüler H. J Biol Chem 299 105096 (2023)
  28. Structure-Based Discovery of Inhibitors of the SARS-CoV-2 Nsp14 N7-Methyltransferase. Singh I, Li F, Fink EA, Chau I, Li A, Rodriguez-Hernández A, Glenn I, Zapatero-Belinchón FJ, Rodriguez ML, Devkota K, Deng Z, White K, Wan X, Tolmachova NA, Moroz YS, Kaniskan HÜ, Ott M, García-Sastre A, Jin J, Fujimori DG, Irwin JJ, Vedadi M, Shoichet BK. J Med Chem 66 7785-7803 (2023)
  29. In Silico Identification and Analysis of Potentially Bioactive Antiviral Phytochemicals against SARS-CoV-2: A Molecular Docking and Dynamics Simulation Approach. Halder SK, Sultana I, Shuvo MN, Shil A, Himel MK, Hasan MA, Shawan MMAK. Biomed Res Int 2023 5469258 (2023)
  30. Letter Of problems and opportunities-How to treat and how to not treat crystallographic fragment screening data. Weiss MS, Wollenhaupt J, Correy GJ, Fraser JS, Heine A, Klebe G, Krojer T, Thunissen M, Pearce NM. Protein Sci 31 e4391 (2022)
  31. SAMPL7 protein-ligand challenge: A community-wide evaluation of computational methods against fragment screening and pose-prediction. Grosjean H, Işık M, Aimon A, Mobley D, Chodera J, von Delft F, Biggin PC. J Comput Aided Mol Des 36 291-311 (2022)
  32. A single inactivating amino acid change in the SARS-CoV-2 NSP3 Mac1 domain attenuates viral replication in vivo. Taha TY, Suryawanshi RK, Chen IP, Correy GJ, McCavitt-Malvido M, O'Leary PC, Jogalekar MP, Diolaiti ME, Kimmerly GR, Tsou CL, Gascon R, Montano M, Martinez-Sobrido L, Krogan NJ, Ashworth A, Fraser JS, Ott M. PLoS Pathog 19 e1011614 (2023)
  33. Allosteric regulation and crystallographic fragment screening of SARS-CoV-2 NSP15 endoribonuclease. Godoy AS, Nakamura AM, Douangamath A, Song Y, Noske GD, Gawriljuk VO, Fernandes RS, Pereira HDM, Oliveira KIZ, Fearon D, Dias A, Krojer T, Fairhead M, Powell A, Dunnet L, Brandao-Neto J, Skyner R, Chalk R, Bajusz D, Bege M, Borbás A, Keserű GM, von Delft F, Oliva G. Nucleic Acids Res 51 5255-5270 (2023)
  34. Discovery and Development Strategies for SARS-CoV-2 NSP3 Macrodomain Inhibitors. Schuller M, Zarganes-Tzitzikas T, Bennett J, De Cesco S, Fearon D, von Delft F, Fedorov O, Brennan PE, Ahel I. Pathogens 12 324 (2023)
  35. Efficient Hit-to-Lead Searching of Kinase Inhibitor Chemical Space via Computational Fragment Merging. Andrianov GV, Gabriel Ong WJ, Serebriiskii I, Karanicolas J. J Chem Inf Model 61 5967-5987 (2021)
  36. Protocol for performing and optimizing differential scanning fluorimetry experiments. Wu T, Hornsby M, Zhu L, Yu JC, Shokat KM, Gestwicki JE. STAR Protoc 4 102688 (2023)
  37. Shedding Light on the Synthesis, Crystal Structure, Characterization, and Computational Study of Optoelectronic Properties and Bioactivity of Imine derivatives. Ashfaq M, Tahir MN, Muhammad S, Munawar KS, Ali S, Ahmed G, Al-Sehemi AG, Alarfaji SS, Ibraheem Khan ME. ACS Omega 7 5217-5230 (2022)
  38. A Fluorescence Polarization Assay for Macrodomains Facilitates the Identification of Potent Inhibitors of the SARS-CoV-2 Macrodomain. Anmangandla A, Jana S, Peng K, Wallace SD, Bagde SR, Drown BS, Xu J, Hergenrother PJ, Fromme JC, Lin H. ACS Chem Biol 18 1200-1207 (2023)
  39. A Small Step Toward Generalizability: Training a Machine Learning Scoring Function for Structure-Based Virtual Screening. Scantlebury J, Vost L, Carbery A, Hadfield TE, Turnbull OM, Brown N, Chenthamarakshan V, Das P, Grosjean H, von Delft F, Deane CM. J Chem Inf Model 63 2960-2974 (2023)
  40. The DarT/DarG Toxin-Antitoxin ADP-Ribosylation System as a Novel Target for a Rational Design of Innovative Antimicrobial Strategies. Catara G, Caggiano R, Palazzo L. Pathogens 12 240 (2023)
  41. Discovery of novel druggable pockets on polyomavirus VP1 through crystallographic fragment-based screening to develop capsid assembly inhibitors. Osipov EM, Munawar AH, Beelen S, Fearon D, Douangamath A, Wild C, Weeks SD, Van Aerschot A, von Delft F, Strelkov SV. RSC Chem Biol 3 1013-1027 (2022)
  42. Experiences From Developing Software for Large X-Ray Crystallography-Driven Protein-Ligand Studies. Pearce NM, Skyner R, Krojer T. Front Mol Biosci 9 861491 (2022)
  43. MBC and ECBL libraries: outstanding tools for drug discovery. Ginex T, Madruga E, Martinez A, Gil C. Front Pharmacol 14 1244317 (2023)
  44. Structure-Based High-Throughput Virtual Screening and Molecular Dynamics Simulation for the Discovery of Novel SARS-CoV-2 NSP3 Mac1 Domain Inhibitors. Yazdani B, Sirous H, Brogi S, Calderone V. Viruses 15 2291 (2023)
  45. Targeting SARS-CoV-2 Macrodomain-1 to Restore the Innate Immune Response Using In Silico Screening of Medicinal Compounds and Free Energy Calculation Approaches. Mohammad A, Alshawaf E, Arefanian H, Marafie SK, Khan A, Wei DQ, Al-Mulla F, Abubaker J. Viruses 15 1907 (2023)
  46. nCoVDock2: a docking server to predict the binding modes between COVID-19 targets and its potential ligands. Liu K, Lu X, Shi H, Xu X, Kong R, Chang S. Nucleic Acids Res 51 W365-W371 (2023)
  47. A Benchmark Study of Protein-Fragment Complex Structure Calculations with NMR2. Torres F, Stadler G, Kwiatkowski W, Orts J. Int J Mol Sci 24 14329 (2023)
  48. Design, quality and validation of the EU-OPENSCREEN fragment library poised to a high-throughput screening collection. Jalencas X, Berg H, Espeland LO, Sreeramulu S, Kinnen F, Richter C, Georgiou C, Yadrykhinsky V, Specker E, Jaudzems K, Miletić T, Harmel R, Gribbon P, Schwalbe H, Brenk R, Jirgensons A, Zaliani A, Mestres J. RSC Med Chem 15 1176-1188 (2024)
  49. Docking for EP4R antagonists active against inflammatory pain. Gahbauer S, DeLeon C, Braz JM, Craik V, Kang HJ, Wan X, Huang XP, Billesbølle CB, Liu Y, Che T, Deshpande I, Jewell M, Fink EA, Kondratov IS, Moroz YS, Irwin JJ, Basbaum AI, Roth BL, Shoichet BK. Nat Commun 14 8067 (2023)
  50. Exploration of piperidine 3D fragment chemical space: synthesis and 3D shape analysis of fragments derived from 20 regio- and diastereoisomers of methyl substituted pipecolinates. Jones SP, Firth JD, Wheldon MC, Atobe M, Hubbard RE, Blakemore DC, De Fusco C, Lucas SCC, Roughley SD, Vidler LR, Whatton MA, Woolford AJ, Wrigley GL, O'Brien P. RSC Med Chem 13 1614-1620 (2022)


Quick links