4awg › Citations

Structural analysis of specific metal chelating inhibitor binding to the endonuclease domain of influenza pH1N1 (2009) polymerase.

Kowalinski E, Zubieta C, Wolkerstorfer A, Szolar OH, Ruigrok RW, Cusack S
PLoS Pathog 8 e1002831 (2012)
Related entries: 4avg, 4avl, 4avq, 4awf, 4awh, 4awk, 4awm

Cited: 88 times
EuropePMC logo PMID: 22876177

Abstract

It is generally recognised that novel antiviral drugs, less prone to resistance, would be a desirable alternative to current drug options in order to be able to treat potentially serious influenza infections. The viral polymerase, which performs transcription and replication of the RNA genome, is an attractive target for antiviral drugs since potent polymerase inhibitors could directly stop viral replication at an early stage. Recent structural studies on functional domains of the heterotrimeric polymerase, which comprises subunits PA, PB1 and PB2, open the way to a structure based approach to optimise inhibitors of viral replication. In particular, the unique cap-snatching mechanism of viral transcription can be inhibited by targeting either the PB2 cap-binding or PA endonuclease domains. Here we describe high resolution X-ray co-crystal structures of the 2009 pandemic H1N1 (pH1N1) PA endonuclease domain with a series of specific inhibitors, including four diketo compounds and a green tea catechin, all of which chelate the two critical manganese ions in the active site of the enzyme. Comparison of the binding mode of the different compounds and that of a mononucleotide phosphate highlights, firstly, how different substituent groups on the basic metal binding scaffold can be orientated to bind in distinct sub-pockets within the active site cavity, and secondly, the plasticity of certain structural elements of the active site cavity, which result in induced fit binding. These results will be important in optimising the design of more potent inhibitors targeting the cap-snatching endonuclease activity of influenza virus polymerase.

Articles - 4awg mentioned but not cited (1)

  1. Structural analysis of specific metal chelating inhibitor binding to the endonuclease domain of influenza pH1N1 (2009) polymerase. Kowalinski E, Zubieta C, Wolkerstorfer A, Szolar OH, Ruigrok RW, Cusack S. PLoS Pathog 8 e1002831 (2012)


Reviews citing this publication (25)

  1. Influenza virus RNA polymerase: insights into the mechanisms of viral RNA synthesis. Te Velthuis AJ, Fodor E. Nat Rev Microbiol 14 479-493 (2016)
  2. Bat-derived influenza-like viruses H17N10 and H18N11. Wu Y, Wu Y, Tefsen B, Shi Y, Gao GF. Trends Microbiol 22 183-191 (2014)
  3. Common and unique features of viral RNA-dependent polymerases. te Velthuis AJ. Cell Mol Life Sci 71 4403-4420 (2014)
  4. Antiviral strategies against influenza virus: towards new therapeutic approaches. Loregian A, Mercorelli B, Nannetti G, Compagnin C, Palù G. Cell Mol Life Sci 71 3659-3683 (2014)
  5. Structural insights into RNA synthesis by the influenza virus transcription-replication machine. Pflug A, Lukarska M, Resa-Infante P, Reich S, Cusack S. Virus Res 234 103-117 (2017)
  6. The Influenza Virus Polymerase Complex: An Update on Its Structure, Functions, and Significance for Antiviral Drug Design. Stevaert A, Naesens L. Med Res Rev 36 1127-1173 (2016)
  7. Targeting the host or the virus: current and novel concepts for antiviral approaches against influenza virus infection. Lee SM, Yen HL. Antiviral Res 96 391-404 (2012)
  8. Towards a structural understanding of RNA synthesis by negative strand RNA viral polymerases. Reguera J, Gerlach P, Cusack S. Curr Opin Struct Biol 36 75-84 (2016)
  9. Structure and assembly of the influenza A virus ribonucleoprotein complex. Zheng W, Tao YJ. FEBS Lett 587 1206-1214 (2013)
  10. Antiviral Mechanism of Action of Epigallocatechin-3-O-gallate and Its Fatty Acid Esters. Kaihatsu K, Yamabe M, Ebara Y. Molecules 23 E2475 (2018)
  11. Antiviral therapies on the horizon for influenza. Naesens L, Stevaert A, Vanderlinden E. Curr Opin Pharmacol 30 106-115 (2016)
  12. New small-molecule drug design strategies for fighting resistant influenza A. Shen Z, Lou K, Wang W. Acta Pharm Sin B 5 419-430 (2015)
  13. Structure and Function of Influenza Polymerase. Wandzik JM, Kouba T, Cusack S. Cold Spring Harb Perspect Med 11 a038372 (2021)
  14. Temperature Sensitive Mutations in Influenza A Viral Ribonucleoprotein Complex Responsible for the Attenuation of the Live Attenuated Influenza Vaccine. Martínez-Sobrido L, Peersen O, Nogales A. Viruses 10 E560 (2018)
  15. Learning from structure-based drug design and new antivirals targeting the ribonucleoprotein complex for the treatment of influenza. Monod A, Swale C, Tarus B, Tissot A, Delmas B, Ruigrok RW, Crépin T, Slama-Schwok A. Expert Opin Drug Discov 10 345-371 (2015)
  16. Computational Molecular Docking and X-ray Crystallographic Studies of Catechins in New Drug Design Strategies. Nakano S, Megro SI, Hase T, Suzuki T, Isemura M, Nakamura Y, Ito S. Molecules 23 E2020 (2018)
  17. Influenza, a One Health paradigm--novel therapeutic strategies to fight a zoonotic pathogen with pandemic potential. Ludwig S, Zell R, Schwemmle M, Herold S. Int J Med Microbiol 304 894-901 (2014)
  18. Crucial role of PA in virus life cycle and host adaptation of influenza A virus. Hu J, Liu X. Med Microbiol Immunol 204 137-149 (2015)
  19. Current Landscape of Antiviral Drug Discovery. Blair W, Cox C. F1000Res 5 F1000 Faculty Rev-202 (2016)
  20. Key Role of the Influenza A Virus PA Gene Segment in the Emergence of Pandemic Viruses. Lutz Iv MM, Dunagan MM, Kurebayashi Y, Takimoto T. Viruses 12 E365 (2020)
  21. Enzymatic Assays to Explore Viral mRNA Capping Machinery. Kasprzyk R, Jemielity J. Chembiochem 22 3236-3253 (2021)
  22. Contemporary medicinal chemistry strategies for the discovery and optimization of influenza inhibitors targeting vRNP constituent proteins. Hou L, Zhang Y, Ju H, Cherukupalli S, Jia R, Zhang J, Huang B, Loregian A, Liu X, Zhan P. Acta Pharm Sin B 12 1805-1824 (2022)
  23. Computational anti-COVID-19 drug design: progress and challenges. Wang J, Zhang Y, Nie W, Luo Y, Deng L. Brief Bioinform 23 bbab484 (2022)
  24. Non-Negligible Role of Trace Elements in Influenza Virus Infection. Xu S, Wang D, Zhao W, Wei Q, Tong Y. Metabolites 13 184 (2023)
  25. Recent Advances in the Phytochemistry of Bryophytes: Distribution, Structures and Biological Activity of Bibenzyl and Bisbibenzyl Compounds. Sen K, Khan MI, Paul R, Ghoshal U, Asakawa Y. Plants (Basel) 12 4173 (2023)

Articles citing this publication (62)

  1. Structure of influenza A polymerase bound to the viral RNA promoter. Pflug A, Guilligay D, Reich S, Cusack S. Nature 516 355-360 (2014)
  2. Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil. Omoto S, Speranzini V, Hashimoto T, Noshi T, Yamaguchi H, Kawai M, Kawaguchi K, Uehara T, Shishido T, Naito A, Cusack S. Sci Rep 8 9633 (2018)
  3. Influenza Polymerase Can Adopt an Alternative Configuration Involving a Radical Repacking of PB2 Domains. Thierry E, Guilligay D, Kosinski J, Bock T, Gaudon S, Round A, Pflug A, Hengrung N, El Omari K, Baudin F, Hart DJ, Beck M, Cusack S. Mol Cell 61 125-137 (2016)
  4. Comparative Structural and Functional Analysis of Bunyavirus and Arenavirus Cap-Snatching Endonucleases. Reguera J, Gerlach P, Rosenthal M, Gaudon S, Coscia F, Günther S, Cusack S. PLoS Pathog 12 e1005636 (2016)
  5. Mutational analysis of the binding pockets of the diketo acid inhibitor L-742,001 in the influenza virus PA endonuclease. Stevaert A, Dallocchio R, Dessì A, Pala N, Rogolino D, Sechi M, Naesens L. J Virol 87 10524-10538 (2013)
  6. Identification of the I38T PA Substitution as a Resistance Marker for Next-Generation Influenza Virus Endonuclease Inhibitors. Jones JC, Kumar G, Barman S, Najera I, White SW, Webby RJ, Govorkova EA. mBio 9 e00430-18 (2018)
  7. Identification and characterization of influenza variants resistant to a viral endonuclease inhibitor. Song MS, Kumar G, Shadrick WR, Zhou W, Jeevan T, Li Z, Slavish PJ, Fabrizio TP, Yoon SW, Webb TR, Webby RJ, White SW. Proc Natl Acad Sci U S A 113 3669-3674 (2016)
  8. Characterization of PA-N terminal domain of Influenza A polymerase reveals sequence specific RNA cleavage. Datta K, Wolkerstorfer A, Szolar OH, Cusack S, Klumpp K. Nucleic Acids Res 41 8289-8299 (2013)
  9. Functional Constraint Profiling of a Viral Protein Reveals Discordance of Evolutionary Conservation and Functionality. Wu NC, Olson CA, Du Y, Le S, Tran K, Remenyi R, Gong D, Al-Mawsawi LQ, Qi H, Wu TT, Sun R. PLoS Genet 11 e1005310 (2015)
  10. Congress Meeting report: 4th ISIRV antiviral group conference: Novel antiviral therapies for influenza and other respiratory viruses. McKimm-Breschkin JL, Fry AM. Antiviral Res 129 21-38 (2016)
  11. Phenyl substituted 4-hydroxypyridazin-3(2H)-ones and 5-hydroxypyrimidin-4(3H)-ones: inhibitors of influenza A endonuclease. Sagong HY, Bauman JD, Patel D, Das K, Arnold E, LaVoie EJ. J Med Chem 57 8086-8098 (2014)
  12. Fragment-Based Identification of Influenza Endonuclease Inhibitors. Credille CV, Chen Y, Cohen SM. J Med Chem 59 6444-6454 (2016)
  13. Influenza A and B viruses with reduced baloxavir susceptibility display attenuated in vitro fitness but retain ferret transmissibility. Jones JC, Pascua PNQ, Fabrizio TP, Marathe BM, Seiler P, Barman S, Webby RJ, Webster RG, Govorkova EA. Proc Natl Acad Sci U S A 117 8593-8601 (2020)
  14. The N-terminal domain of PA from bat-derived influenza-like virus H17N10 has endonuclease activity. Tefsen B, Lu G, Zhu Y, Haywood J, Zhao L, Deng T, Qi J, Gao GF. J Virol 88 1935-1941 (2014)
  15. A novel small-molecule inhibitor of influenza A virus acts by suppressing PA endonuclease activity of the viral polymerase. Yuan S, Chu H, Singh K, Zhao H, Zhang K, Kao RY, Chow BK, Zhou J, Zheng BJ. Sci Rep 6 22880 (2016)
  16. N-acylhydrazone inhibitors of influenza virus PA endonuclease with versatile metal binding modes. Carcelli M, Rogolino D, Gatti A, De Luca L, Sechi M, Kumar G, White SW, Stevaert A, Naesens L. Sci Rep 6 31500 (2016)
  17. Amino acid substitutions V63I or A37S/I61T/V63I/V100A in the PA N-terminal domain increase the virulence of H7N7 influenza A virus. Hu M, Chu H, Zhang K, Singh K, Li C, Yuan S, Chow BK, Song W, Zhou J, Zheng BJ. Sci Rep 6 37800 (2016)
  18. Structure of a functional cap-binding domain in Rift Valley fever virus L protein. Gogrefe N, Reindl S, Günther S, Rosenthal M. PLoS Pathog 15 e1007829 (2019)
  19. The Cap-Snatching SFTSV Endonuclease Domain Is an Antiviral Target. Wang W, Shin WJ, Zhang B, Choi Y, Yoo JS, Zimmerman MI, Frederick TE, Bowman GR, Gross ML, Leung DW, Jung JU, Amarasinghe GK. Cell Rep 30 153-163.e5 (2020)
  20. The RNA-dependent RNA polymerase of the influenza A virus. Stubbs TM, Te Velthuis AJ. Future Virol 9 863-876 (2014)
  21. Atomic Structure and Biochemical Characterization of an RNA Endonuclease in the N Terminus of Andes Virus L Protein. Fernández-García Y, Reguera J, Busch C, Witte G, Sánchez-Ramos O, Betzel C, Cusack S, Günther S, Reindl S. PLoS Pathog 12 e1005635 (2016)
  22. Biochemical and structural studies reveal differences and commonalities among cap-snatching endonucleases from segmented negative-strand RNA viruses. Holm T, Kopicki JD, Busch C, Olschewski S, Rosenthal M, Uetrecht C, Günther S, Reindl S. J Biol Chem 293 19686-19698 (2018)
  23. Investigation of the salicylaldehyde thiosemicarbazone scaffold for inhibition of influenza virus PA endonuclease. Rogolino D, Bacchi A, De Luca L, Rispoli G, Sechi M, Stevaert A, Naesens L, Carcelli M. J Biol Inorg Chem 20 1109-1121 (2015)
  24. Amino acid changes in the influenza A virus PA protein that attenuate avian H5N1 viruses in mammals. Fan S, Hatta M, Kim JH, Le MQ, Neumann G, Kawaoka Y. J Virol 88 13737-13746 (2014)
  25. An integrated biological approach to guide the development of metal-chelating inhibitors of influenza virus PA endonuclease. Stevaert A, Nurra S, Pala N, Carcelli M, Rogolino D, Shepard C, Domaoal RA, Kim B, Alfonso-Prieto M, Marras SA, Sechi M, Naesens L. Mol Pharmacol 87 323-337 (2015)
  26. Capped RNA primer binding to influenza polymerase and implications for the mechanism of cap-binding inhibitors. Pflug A, Gaudon S, Resa-Infante P, Lethier M, Reich S, Schulze WM, Cusack S. Nucleic Acids Res 46 956-971 (2018)
  27. Chemical Genomics Identifies the PERK-Mediated Unfolded Protein Stress Response as a Cellular Target for Influenza Virus Inhibition. Landeras-Bueno S, Fernández Y, Falcón A, Oliveros JC, Ortín J. mBio 7 e00085-16 (2016)
  28. Targeting Importin-α7 as a Therapeutic Approach against Pandemic Influenza Viruses. Resa-Infante P, Paterson D, Bonet J, Otte A, Oliva B, Fodor E, Gabriel G. J Virol 89 9010-9020 (2015)
  29. Comparative structural and functional analysis of orthomyxovirus polymerase cap-snatching domains. Guilligay D, Kadlec J, Crépin T, Lunardi T, Bouvier D, Kochs G, Ruigrok RW, Cusack S. PLoS One 9 e84973 (2014)
  30. Toosendanin From Melia Fructus Suppresses Influenza A Virus Infection by Altering Nuclear Localization of Viral Polymerase PA Protein. Jin YH, Kwon S, Choi JG, Cho WK, Lee B, Ma JY. Front Pharmacol 10 1025 (2019)
  31. Identification of Amino Acid Residues in Influenza A Virus PA-X That Contribute to Enhanced Shutoff Activity. Oishi K, Yamayoshi S, Kawaoka Y. Front Microbiol 10 432 (2019)
  32. Novel Ranking System for Identifying Efficacious Anti-Influenza Virus PB2 Inhibitors. Tsai AW, McNeil CF, Leeman JR, Bennett HB, Nti-Addae K, Huang C, Germann UA, Byrn RA, Berlioz-Seux F, Rijnbrand R, Clark MP, Charifson PS, Jones SM. Antimicrob Agents Chemother 59 6007-6016 (2015)
  33. Structural insights into the substrate specificity of the endonuclease activity of the influenza virus cap-snatching mechanism. Kumar G, Cuypers M, Webby RR, Webb TR, White SW. Nucleic Acids Res 49 1609-1618 (2021)
  34. The Surface-Exposed PA51-72-Loop of the Influenza A Virus Polymerase Is Required for Viral Genome Replication. Nilsson-Payant BE, Sharps J, Hengrung N, Fodor E. J Virol 92 e00687-18 (2018)
  35. Thermodynamic and computational analyses reveal the functional roles of the galloyl group of tea catechins in molecular recognition. Takahashi T, Nagatoishi S, Kuroda D, Tsumoto K. PLoS One 13 e0204856 (2018)
  36. Crystal structures of Lymphocytic choriomeningitis virus endonuclease domain complexed with diketo-acid ligands. Saez-Ayala M, Yekwa EL, Carcelli M, Canard B, Alvarez K, Ferron F. IUCrJ 5 223-235 (2018)
  37. Protein-Structure Assisted Optimization of 4,5-Dihydroxypyrimidine-6-Carboxamide Inhibitors of Influenza Virus Endonuclease. Beylkin D, Kumar G, Zhou W, Park J, Jeevan T, Lagisetti C, Harfoot R, Webby RJ, White SW, Webb TR. Sci Rep 7 17139 (2017)
  38. AZT acts as an anti-influenza nucleotide triphosphate targeting the catalytic site of A/PR/8/34/H1N1 RNA dependent RNA polymerase. Pagadala NS. J Comput Aided Mol Des 33 387-404 (2019)
  39. An RNA Hybridization Assay for Screening Influenza A Virus Polymerase Inhibitors Using the Entire Ribonucleoprotein Complex. Roch FF, Hinterkörner G, Menke J, Tang GQ, Cusack S, Butzendobler B, Buschmann H, Datta K, Wolkerstorfer A. Assay Drug Dev Technol 13 488-506 (2015)
  40. Design of the influenza virus inhibitors targeting the PA endonuclease using 3D-QSAR modeling, side-chain hopping, and docking. Yan Z, Zhang L, Fu H, Wang Z, Lin J. Bioorg Med Chem Lett 24 539-547 (2014)
  41. Epigallocatechin-3-Gallate (EGCG) Inhibits SARS-CoV-2 Infection in Primate Epithelial Cells: (A Short Communication). Hurst BL, Dickinson D, Hsu S. Microbiol Infect Dis 5 (2021)
  42. Multiple polymerase acidic (PA) I38X substitutions in influenza A(H1N1)pdm09 virus permit polymerase activity and cause reduced baloxavir inhibition. Jones JC, Pascua PNQ, Harrington WN, Webby RJ, Govorkova EA. J Antimicrob Chemother 76 957-960 (2021)
  43. Synthesis of 1,2,3-triazolyl nucleoside analogues and their antiviral activity. Andreeva OV, Garifullin BF, Zarubaev VV, Slita AV, Yesaulkova IL, Saifina LF, Shulaeva MM, Belenok MG, Semenov VE, Kataev VE. Mol Divers 25 473-490 (2021)
  44. Molecular features of influenza A (H1N1)pdm09 prevalent in Mexico during winter seasons 2012-2014. Arellano-Llamas R, Alfaro-Ruiz L, Arriaga Canon C, Imaz Rosshandler I, Cruz-Lagunas A, Zúñiga J, Rebollar Vega R, Wong CW, Maurer-Stroh S, Romero Córdoba S, Liu ET, Hidalgo-Miranda A, Vázquez-Pérez JA. PLoS One 12 e0180419 (2017)
  45. PAN substitutions A37S, A37S/I61T and A37S/V63I attenuate the replication of H7N7 influenza A virus by impairing the polymerase and endonuclease activities. Hu M, Yuan S, Ye ZW, Singh K, Li C, Shuai H, Fai N, Chow BKC, Chu H, Zheng BJ. J Gen Virol 98 364-373 (2017)
  46. Structural analysis of H1N1 and H7N9 influenza A virus PA in the absence of PB1. Moen SO, Abendroth J, Fairman JW, Baydo RO, Bullen J, Kirkwood JL, Barnes SR, Raymond AC, Begley DW, Henkel G, McCormack K, Tam VC, Phan I, Staker BL, Stacy R, Myler PJ, Lorimer D, Edwards TE. Sci Rep 4 5944 (2014)
  47. Synthesis and In Vitro Evaluation of C-7 and C-8 Luteolin Derivatives as Influenza Endonuclease Inhibitors. Reiberger R, Radilová K, Kráľ M, Zima V, Majer P, Brynda J, Dračínský M, Konvalinka J, Kožíšek M, Machara A. Int J Mol Sci 22 7735 (2021)
  48. The ubiquitination landscape of the influenza A virus polymerase. Günl F, Krischuns T, Schreiber JA, Henschel L, Wahrenburg M, Drexler HCA, Leidel SA, Cojocaru V, Seebohm G, Mellmann A, Schwemmle M, Ludwig S, Brunotte L. Nat Commun 14 787 (2023)
  49. Dipeptidyl Peptidase-4 Is a Target Protein of Epigallocatechin-3-Gallate. Hou H, Wang Y, Li C, Wang J, Cao Y. Biomed Res Int 2020 5370759 (2020)
  50. Insights into Two-Metal-Ion Catalytic Mechanism of Cap-Snatching Endonuclease of Ebinur Lake Virus in Bunyavirales. Kuang W, Zhang H, Cai Y, Zhang G, Deng F, Li H, Hu Z, Guo Y, Wang M, Zhou Y, Gong P. J Virol 96 e0208521 (2022)
  51. New Insight into Metal Ion-Driven Catalysis of Nucleic Acids by Influenza PA-Nter. Kotlarek D, Worch R. PLoS One 11 e0156972 (2016)
  52. Stacking with No Planarity? Gunaydin H, Bartberger MD. ACS Med Chem Lett 7 341-344 (2016)
  53. siRNAs targeting PB2 and NP genes potentially inhibit replication of Highly Pathogenic H5N1 Avian Influenza Virus. Behera P, Nagarajan S, Murugkar HV, Kalaiyarasu S, Prakash A, Gothalwal R, Dubey SC, Kulkarni DD, Tosh C. J Biosci 40 233-240 (2015)
  54. Aryl and Arylalkyl Substituted 3-Hydroxypyridin-2(1H)-ones: Synthesis and Evaluation as Inhibitors of Influenza A Endonuclease. Sagong HY, Bauman JD, Nogales A, Martínez-Sobrido L, Arnold E, LaVoie EJ. ChemMedChem 14 1204-1223 (2019)
  55. The First 5'-Phosphorylated 1,2,3-Triazolyl Nucleoside Analogues with Uracil and Quinazoline-2,4-Dione Moieties: A Synthesis and Antiviral Evaluation. Tatarinov DA, Garifullin BF, Belenok MG, Andreeva OV, Strobykina IY, Shepelina AV, Zarubaev VV, Slita AV, Volobueva AS, Saifina LF, Shulaeva MM, Semenov VE, Kataev VE. Molecules 27 6214 (2022)
  56. Computational analysis of the effect of polymerase acidic (PA) gene mutation F35L in the 2009 pandemic influenza A (H1N1) virus on binding aspects of mononucleotides in the endonuclease domain. Bhoye D, Cherian SS. Arch Virol 163 1031-1036 (2018)
  57. Exploration of the 2,3-dihydroisoindole pharmacophore for inhibition of the influenza virus PA endonuclease. Rogolino D, Naesens L, Bartoli J, Carcelli M, De Luca L, Pelosi G, Stokes RW, Van Berwaer R, Vittorio S, Stevaert A, Cohen SM. Bioorg Chem 116 105388 (2021)
  58. Salicylate metal-binding isosteres as fragments for metalloenzyme inhibition. Jackl MK, Seo H, Karges J, Kalaj M, Cohen SM. Chem Sci 13 2128-2136 (2022)
  59. Structural and Biochemical Basis for Development of Diketo Acid Inhibitors Targeting the Cap-Snatching Endonuclease of the Ebinur Lake Virus (Order: Bunyavirales). Kuang W, Zhang H, Cai Y, Zhang G, Deng F, Li H, Zhou Y, Wang M, Gong P, Guo Y, Hu Z. J Virol 96 e0217321 (2022)
  60. A novel compound to overcome influenza drug resistance in endonuclease inhibitors. Ren Y, Wan L, Cao S. Mol Divers (2023)
  61. The impact of PA/I38 substitutions and PA polymorphisms on the susceptibility of zoonotic influenza A viruses to baloxavir. Taniguchi K, Noshi T, Omoto S, Sato A, Shishido T, Matsuno K, Okamatsu M, Krauss S, Webby RJ, Sakoda Y, Kida H. Arch Virol 169 29 (2024)
  62. Understanding the Structure-Activity Relationship through Density Functional Theory: A Simple Method Predicts Relative Binding Free Energies of Metalloenzyme Fragment-like Inhibitors. Vasile S, Roos K. ACS Omega 8 21438-21449 (2023)


Quick links