Advertisement

Comparison of affinity ranking using AutoDock-GPU and MM-GBSA scores for BACE-1 inhibitors in the D3R Grand Challenge 4

  • Léa El Khoury
  • Diogo Santos-Martins
  • Sukanya Sasmal
  • Jérôme Eberhardt
  • Giulia Bianco
  • Francesca Alessandra Ambrosio
  • Leonardo Solis-Vasquez
  • Andreas Koch
  • Stefano ForliEmail author
  • David L. MobleyEmail author
Article

Abstract

Molecular docking has been successfully used in computer-aided molecular design projects for the identification of ligand poses within protein binding sites. However, relying on docking scores to rank different ligands with respect to their experimental affinities might not be sufficient. It is believed that the binding scores calculated using molecular mechanics combined with the Poisson–Boltzman surface area (MM-PBSA) or generalized Born surface area (MM-GBSA) can predict binding affinities more accurately. In this perspective, we decided to take part in Stage 2 of the Drug Design Data Resource (D3R) Grand Challenge 4 (GC4) to compare the performance of a quick scoring function, AutoDock4, to that of MM-GBSA in predicting the binding affinities of a set of \(\beta\)-Amyloid Cleaving Enzyme 1 (BACE-1) ligands. Our results show that re-scoring docking poses using MM-GBSA did not improve the correlation with experimental affinities. We further did a retrospective analysis of the results and found that our MM-GBSA protocol is sensitive to details in the protein-ligand system: (i) neutral ligands are more adapted to MM-GBSA calculations than charged ligands, (ii) predicted binding affinities depend on the initial conformation of the BACE-1 receptor, (iii) protonating the aspartyl dyad of BACE-1 correctly results in more accurate binding affinity predictions.

Keywords

Docking MM-GBSA AutoDock Scoring functions 

Notes

Acknowledgements

SS, LEK and DM thank Christopher I. Bayly (OpenEye Scientific Software) for helpful discussions on MM-GBSA calculations. SS, LEK and DM also acknowledge OpenEye Scientific Software for licensing the pieces of software used in this work. The National Institutes of Health supported this work through grants 1R01GM108889-01 (DLM), R01 GM069832 (DSM, JE, SF) and U54-GM103368 (GB). LSV and AK thank the German Academic Exchange Service (DAAD) and the Peruvian National Program for Scholarships and Educational Loans (PRONABEC) for financial aid.

Supplementary material

10822_2019_240_MOESM1_ESM.pdf (91 kb)
Electronic supplementary material 1 (PDF 91 kb)

References

  1. 1.
    Kitchen DB, Decornez H, Furr JR, Bajorath J (2004) Nat Rev Drug Discov 3(11):935.  https://doi.org/10.1038/nrd1549 CrossRefPubMedGoogle Scholar
  2. 2.
    Heikamp K, Bajorath J (2013) Chem Biol Drug Des 81(1):33.  https://doi.org/10.1111/cbdd.12054 CrossRefPubMedGoogle Scholar
  3. 3.
    Gilson MK, Zhou HX (2007) Annu Rev Biophys Biomol Struct 36(1):21.  https://doi.org/10.1146/annurev.biophys.36.040306.132550 CrossRefPubMedGoogle Scholar
  4. 4.
    Gaieb Z, Parks CD, Chiu M, Yang H, Shao C, Walters WP, Lambert MH, Nevins N, Bembenek SD, Ameriks MK, Mirzadegan T, Burley SK, Amaro RE, Gilson MK (2019) J Comput Aided Mol Des 33(1):1.  https://doi.org/10.1007/s10822-018-0180-4 CrossRefPubMedGoogle Scholar
  5. 5.
    Yin J, Henriksen NM, Slochower DR, Shirts MR, Chiu MW, Mobley DL, Gilson MK (2017) J Comput Aided Mol Des 31(1):1.  https://doi.org/10.1007/s10822-016-9974-4 CrossRefPubMedGoogle Scholar
  6. 6.
    Vassar R, Bennett BD, Babu-Khan S, Kahn S, Mendiaz EA, Denis P, Teplow DB, Ross S, Amarante P, Loeloff R, Luo Y, Fisher S, Fuller J, Edenson S, Lile J, Jarosinski MA, Biere AL, Curran E, Burgess T, Louis JC, Collins F, Treanor J, Rogers G, Citron M (1999) Science 286(5440):735.  https://doi.org/10.1126/science.286.5440.735 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Genheden S, Ryde U (2015) Expert Opin Drug Discov 10(5):449.  https://doi.org/10.1517/17460441.2015.1032936 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Kollman PA, Massova I, Reyes C, Kuhn B, Huo S, Chong L, Lee M, Lee T, Duan Y, Wang W, Donini O, Cieplak P, Srinivasan J, Case DA, Cheatham TE (2000) Acc Chem Res 33(12):889.  https://doi.org/10.1021/ar000033j CrossRefPubMedGoogle Scholar
  9. 9.
    Kaus JW, Harder E, Lin T, Abel R, McCammon JA, Wang L (2015) J Chem Theory Comput 11(6):2670.  https://doi.org/10.1021/acs.jctc.5b00214 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Hou T, Wang J, Li Y, Wang W (2010) J Chem Inf Model 51(1):69.  https://doi.org/10.1039/c4cp01388c CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Greenidge PA, Kramer C, Mozziconacci JC, Sherman W (2014) J Chem Inf Model 54(10):2697.  https://doi.org/10.1021/ci5003735 PMID: 25266271CrossRefPubMedGoogle Scholar
  12. 12.
    Wang C, Greene D, Xiao L, Qi R, Luo R (2018) Front Mol Biosci 4:87.  https://doi.org/10.3389/fmolb.2017.00087 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Slynko I, Scharfe M, Rumpf T, Eib J, Metzger E, Schüle R, Jung M, Sippl W (2014) J Chem Inf Model 54(1):138.  https://doi.org/10.1021/ci400628q PMID: 24377786CrossRefPubMedGoogle Scholar
  14. 14.
    Sun H, Li Y, Shen M, Tian S, Xu L, Pan P, Guan Y, Hou T (2014) Phys Chem Chem Phys 16:22035.  https://doi.org/10.1039/C4CP03179B CrossRefPubMedGoogle Scholar
  15. 15.
    Rastelli G, Del Rio A, Degliesposti G, Sgobba M (2010) J Comput Chem 31(4):797.  https://doi.org/10.1002/jcc.21372 CrossRefPubMedGoogle Scholar
  16. 16.
    Réau M, Langenfeld F, Zagury JF, Montes M (2018) J Comput Aided Mol Des 32(1):231.  https://doi.org/10.1007/s10822-017-0063-0 CrossRefPubMedGoogle Scholar
  17. 17.
    Misini Ignjatović M, Caldararu O, Dong G, Muñoz-Gutierrez C, Adasme-Carreño F, Ryde U (2016) J Comput Aided Mol Des 30(9):707.  https://doi.org/10.1007/s10822-016-9942-z CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Salmaso V, Sturlese M, Cuzzolin A, Moro S (2018) J Comput Aided Mol Des 32(1):251.  https://doi.org/10.1007/s10822-017-0051-4 CrossRefPubMedGoogle Scholar
  19. 19.
    Huey R, Morris GM, Olson AJ, Goodsell DS (2007) J Comput Chem 28(6):1145CrossRefGoogle Scholar
  20. 20.
    Stouten PF, Frömmel C, Nakamura H, Sander C (1993) Mol Simul 10(2–6):97CrossRefGoogle Scholar
  21. 21.
    Gasteiger J, Marsili M (1980) Tetrahedron 36(22):3219CrossRefGoogle Scholar
  22. 22.
    Jakalian A, Jack DB, Bayly CI (2002) J Comput Chem 23(16):1623.  https://doi.org/10.1002/jcc.10128 CrossRefPubMedGoogle Scholar
  23. 23.
    Lyne PD, Lamb ML, Saeh JC (2006) J Med Chem 49(16):4805.  https://doi.org/10.1021/jm060522a CrossRefPubMedGoogle Scholar
  24. 24.
    Su PC, Tsai CC, Mehboob S, Hevener KE, Johnson ME (2015) J Comput Chem 36(25):1859.  https://doi.org/10.1002/jcc.24011 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Huang SY, Grinter SZ, Zou X (2010) Phys Chem Chem Phys 12(40):12899.  https://doi.org/10.1039/C0CP00151A CrossRefPubMedGoogle Scholar
  26. 26.
  27. 27.
    Chang CE, Chen W, Gilson MK (2005) J Chem Theory Comput 1(5):1017.  https://doi.org/10.1021/ct0500904 CrossRefPubMedGoogle Scholar
  28. 28.
    Brooks BR, Janežič D, Karplus M (1995) J Comput Chem 16(12):1522.  https://doi.org/10.1002/jcc.540161209 CrossRefGoogle Scholar
  29. 29.
    Santos-Martins D, Solis-Vasquez L, Koch A, Forli S (2019).  https://doi.org/10.26434/chemrxiv.9702389.v1
  30. 30.
    Zeiler MD (2012) arXiv preprint arXiv:1212.5701
  31. 31.
    O’Boyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR (2011) J Cheminformatics 3(1):33CrossRefGoogle Scholar
  32. 32.
    O’Boyle NM, Morley C, Hutchison GR (2008) Chem Cent J 2(1):5CrossRefGoogle Scholar
  33. 33.
    Word JM, Lovell SC, Richardson JS, Richardson DC (1999) J Mol Biol 285(4):1735CrossRefGoogle Scholar
  34. 34.
    Forli S, Huey R, Pique ME, Sanner MF, Goodsell DS, Olson AJ (2016) Nat Protoc 11(5):905CrossRefGoogle Scholar
  35. 35.
    O’Boyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR (2011) J Cheminformatics 3(1):33CrossRefGoogle Scholar
  36. 36.
    Santos-Martins D, Eberhardt J, Bianco G, Solis-Vasquez L, Ambrosio FA, Koch A, Forli S (Accepted for the same issue. Manuscript number: JCAM-D-19-00134) Title: D3R Grand Challenge 4: prospective pose prediction of BACE1 ligands with AutoDock-GPUGoogle Scholar
  37. 37.
    Case D, Brozell S, Cerutti D, Cheatham TI, Cruzeiro V, Darden T, Duke R, Ghoreishi D, Gohlke H, Goetz A, Greene D, Harris R, Homeyer N, Izadi S, Kovalenko A, Lee T, LeGrand S, Li P, Lin C, Liu J, Luchko T, Luo R, Mermelstein D, Merz K, Miao Y, Monard G, Nguyen H, Omelyan I, Onufriev A, Pan F, Qi R, Roe D, Roitberg A, Sagui C, Schott-Verdugo S, Shen J, Simmerling C, Smith J, Swails J, Walker R, Wang J, Wei H, Wolf R, Wu X, Xiao L, York D, Kollman P (2018) Amber 2018, University of California, San FranciscoGoogle Scholar
  38. 38.
    Case D, Cerutti D, Cheateham T, Darden T, Duke R, Giese T, Gohlke H, Goetz A, Greene D, Homeyer N, Simmerling C, Botello-Smith W, Swail J, Walker R, Wang J, Wolf R, Wu X, Xiao L, Kollman P (2016) Amber 2016, University of California, San FranciscoGoogle Scholar
  39. 39.
    Hornak V, Abel R, Okur A, Strockbine B, Roitberg A, Simmerling C (2006) Proteins Struct Funct Bioinf 65:712.  https://doi.org/10.1002/prot.21123 CrossRefGoogle Scholar
  40. 40.
    Wang J, Wolf RM, Caldwell JW, Kollman PA, Case DA (2004) J Comput Chem 25(9):1157.  https://doi.org/10.1002/jcc.20035 CrossRefPubMedGoogle Scholar
  41. 41.
    Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML (1983) J Chem Phys 79(2):926.  https://doi.org/10.1063/1.445869 CrossRefGoogle Scholar
  42. 42.
    Miller BR, McGee TD, Swails JM, Homeyer N, Gohlke H, Roitberg AE (2012) J Chem Theory Comput 8(9):3314.  https://doi.org/10.1021/ct300418h CrossRefPubMedGoogle Scholar
  43. 43.
    Nguyen H, Roe DR, Simmerling C (2013) J Chem Theory Comput 9(4):2020.  https://doi.org/10.1021/ct3010485 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Shimizu H, Tosaki A, Kaneko K, Hisano T, Sakurai T, Nukina N (2008) Mol Cell Biol 28(11):3663.  https://doi.org/10.1128/MCB.02185-07 CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Ellis CR, Tsai CC, Hou X, Shen J (2016) J Phys Chem Lett 7(6):944.  https://doi.org/10.1021/acs.jpclett.6b00137 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Kim MO, Blachly PG, McCammon JA (2015) PLoS Comput Biol 11(10):1.  https://doi.org/10.1371/journal.pcbi.1004341 CrossRefGoogle Scholar
  47. 47.
    Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) J Comput Chem 25(13):1605.  https://doi.org/10.1002/jcc.20084 CrossRefPubMedGoogle Scholar
  48. 48.
    Ravindranath PA, Forli S, Goodsell DS, Olson AJ, Sanner MF (2015) PLoS Comput Biol 11(12):e1004586CrossRefGoogle Scholar
  49. 49.
    Feig M, Onufriev A, Lee MS, Im W, Case DA, Brooks CL III (2004) J Comput Chem 25(2):265.  https://doi.org/10.1002/jcc.10378 CrossRefPubMedGoogle Scholar
  50. 50.
    Onufriev A, Bashford D, Case DA (2004) Proteins Struct Funct Bioinf 55(2):383.  https://doi.org/10.1002/prot.20033 CrossRefGoogle Scholar
  51. 51.
    Srivastava HK, Sastry GN (2012) J Chem Inf Model 52(11):3088.  https://doi.org/10.1021/ci300385h CrossRefPubMedGoogle Scholar
  52. 52.
    Shirts MR, Mobley DL, Brown SP (2010) Drug design: structure-and ligand-based approaches, pp 61–86Google Scholar
  53. 53.
    Niu Y, Yao X, Ji H (2019) RSC Adv 9(22):12441.  https://doi.org/10.1039/C9RA01657K CrossRefGoogle Scholar
  54. 54.
    Hu S, Dong Y, Zhao X, Zhang L (2019) J Mol Graph Model.  https://doi.org/10.1016/j.jmgm.2019.03.022 CrossRefGoogle Scholar
  55. 55.
    Mishra SK, Koca J (2018) J Phys Chem B 122(34):8113.  https://doi.org/10.1021/acs.jpcb.8b03655 CrossRefPubMedGoogle Scholar
  56. 56.
    Onufriev A, Bashford D, Case DA (2004) Proteins 55(2):383.  https://doi.org/10.1002/prot.20033 CrossRefPubMedGoogle Scholar
  57. 57.
    Li J, Abel R, Zhu K, Cao Y, Zhao S, Friesner RA (2011) Proteins 79(10):2794.  https://doi.org/10.1002/prot.23106 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Pharmaceutical SciencesUniversity of California, IrvineIrvineUSA
  2. 2.Department of Integrative Structural and Computational BiologyThe Scripps Research InstituteLa JollaUSA
  3. 3.Department of Health Sciences“Magna Græcia” University of CatanzaroCatanzaroItaly
  4. 4.Embedded Systems and Applications GroupTechnische Universität DarmstadtDarmstadtGermany
  5. 5.Department of ChemistryUniversity of California, IrvineIrvineUSA

Personalised recommendations