Skip to main content
SpringerLink
Log in

Homology Modeling of Protein Targets with MODELLER

  • Protocol
  • First Online:
Docking Screens for Drug Discovery

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2053))

Abstract

Homology modeling is a computational approach to generate three-dimensional structures of protein targets when experimental data about similar proteins are available. Although experimental methods such as X-ray crystallography and nuclear magnetic resonance spectroscopy successfully solved the structures of nearly 150,000 macromolecules, there is still a gap in our structural knowledge. We can fulfill this gap with computational methodologies. Our goal in this chapter is to explain how to perform homology modeling of protein targets for drug development. We choose as a homology modeling tool the program MODELLER. To illustrate its use, we describe how to model the structure of human cyclin-dependent kinase 3 using MODELLER. We explain the modeling procedure of CDK3 apoenzyme and the structure of this enzyme in complex with roscovitine.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Filgueira de Azevedo W Jr, dos Santos GC, dos Santos DM, Olivieri JR, Canduri F, Silva RG et al (2003) Docking and small angle X-ray scattering studies of purine nucleoside phosphorylase. Biochem Biophys Res Commun 309:923–928

    Article  CAS  PubMed  Google Scholar 

  2. da Silveira NJ, Arcuri HA, Bonalumi CE, de Souza FP, Mello IM, Rahal P et al (2005) Molecular models of NS3 protease variants of the hepatitis C virus. BMC Struct Biol 5:1

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Silveira NJ, Uchôa HB, Pereira JH, Canduri F, Basso LA, Palma MS et al (2005) Molecular models of protein targets from Mycobacterium tuberculosis. J Mol Model 11:160–166

    Article  CAS  PubMed  Google Scholar 

  4. da Silveira NJ, Bonalumi CE, Uchõa HB, Pereira JH, Canduri F, de Azevedo WF (2006) DBMODELING: a database applied to the study of protein targets from genome projects. Cell Biochem Biophys 44:366–374

    Article  PubMed  Google Scholar 

  5. da Silveira NJF, Bonalumi CE, Arcuri HA, de Azevedo WF Jr (2007) Molecular modeling databases: a new way in the search of proteins targets for drug development. Curr Bioinforma 2:1–10

    Article  Google Scholar 

  6. Marques MR, Pereira JH, Oliveira JS, Basso LA, de Azevedo WF Jr, Santos DS et al (2007) The inhibition of 5-enolpyruvylshikimate-3-phosphate synthase as a model for development of novel antimicrobials. Curr Drug Targets 8:445–457

    Article  CAS  PubMed  Google Scholar 

  7. Breda A, Basso LA, Santos DS, de Azevedo WF Jr (2008) Virtual screening of drugs: score functions, docking, and drug design. Curr Comput Aided Drug Des 4:265–272

    Article  CAS  Google Scholar 

  8. de Azevedo WF Jr, Dias R (2008) Computational methods for calculation of ligand-binding affinity. Curr Drug Targets 9:1031–1039

    Article  PubMed  Google Scholar 

  9. Dias R, de Azevedo WF Jr (2008) Molecular docking algorithms. Curr Drug Targets 9:1040–1047

    Article  CAS  PubMed  Google Scholar 

  10. Arcuri HA, Zafalon GF, Marucci EA, Bonalumi CE, da Silveira NJ, Machado JM et al (2010) SKPDB: a structural database of shikimate pathway enzymes. BMC Bioinformatics 11:12

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. De Azevedo WF Jr (2010) MolDock applied to structure-based virtual screening. Curr Drug Targets 11:327–334

    Article  PubMed  Google Scholar 

  12. Ducati RG, Basso LA, Santos DS, de Azevedo WF Jr (2010) Crystallographic and docking studies of purine nucleoside phosphorylase from Mycobacterium tuberculosis. Bioorg Med Chem 18:4769–4774

    Article  CAS  PubMed  Google Scholar 

  13. Heberlé G, de Azevedo WF Jr (2011) Bio-inspired algorithms applied to molecular docking simulations. Curr Med Chem 18:1339–1352

    Article  PubMed  Google Scholar 

  14. Rocha BA, Delatorre P, Oliveira TM, Benevides RG, Pires AF, Sousa AA et al (2011) Structural basis for both pro- and anti-inflammatory response induced by mannose-specific legume lectin from Cymbosema roseum. Biochimie 93:806–816

    Article  CAS  PubMed  Google Scholar 

  15. Vianna CP, de Azevedo WF Jr (2012) Identification of new potential Mycobacterium tuberculosis shikimate kinase inhibitors through molecular docking simulations. J Mol Model 18:755–764

    Article  CAS  PubMed  Google Scholar 

  16. Moraes FP, de Azevedo WF Jr (2012) Targeting imidazoline site on monoamine oxidase B through molecular docking simulations. J Mol Model 18:3877–3886

    Article  CAS  PubMed  Google Scholar 

  17. Azevedo LS, Moraes FP, Xavier MM, Pantoja EO, Villavicencio B, Finck JA et al (2012) Recent Progress of molecular docking simulations applied to development of drugs. Curr Bioinforma 7:352–365

    Article  CAS  Google Scholar 

  18. Coracini JD, de Azevedo WF Jr (2014) Shikimate kinase, a protein target for drug design. Curr Med Chem 21:592–604

    Article  CAS  PubMed  Google Scholar 

  19. de Avila MB, de Azevedo WF (2014) Data Mining of Docking Results. Application to 3-Dehydroquinate Dehydratase. Curr Bioinforma 9:361–379

    Article  CAS  Google Scholar 

  20. Teles CB, Moreira-Dill LS, Silva Ade A, Facundo VA, de Azevedo WF Jr, da Silva LH et al (2015) A lupane-triterpene isolated from Combretum leprosum Mart. fruit extracts that interferes with the intracellular development of Leishmania (L.) amazonensis in vitro. BMC Complement Altern Med 15:165

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. de Azevedo WF Jr (2016) Opinion paper: targeting multiple cyclin-dependent kinases (CDKs): a new strategy for molecular docking studies. Curr Drug Targets 17:2

    Article  PubMed  CAS  Google Scholar 

  22. Canduri F, de Azevedo WF (2008) Protein crystallography in drug discovery. Curr Drug Targets 9:1048–1053

    Article  CAS  PubMed  Google Scholar 

  23. Fadel V, Bettendorff P, Herrmann T, de Azevedo WF Jr, Oliveira EB, Yamane T et al (2005) Automated NMR structure determination and disulfide bond identification of the myotoxin crotamine from Crotalus durissus terrificus. Toxicon 46:759–767

    Article  CAS  PubMed  Google Scholar 

  24. Heck GS, Pintro VO, Pereira RR, de Ávila MB, Levin NMB, de Azevedo WF (2017) Supervised machine learning methods applied to predict ligand-binding affinity. Curr Med Chem 24:2459–2470

    Article  CAS  PubMed  Google Scholar 

  25. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H et al (2000) The Protein Data Bank. Nucleic Acids Res 28:235–242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Berman HM, Battistuz T, Bhat TN, Bluhm WF, Bourne PE, Burkhardt K et al (2002) The Protein Data Bank. Acta Crystallogr D Biol Crystallogr 58:899–907

    Article  CAS  PubMed  Google Scholar 

  27. Westbrook J, Feng Z, Chen L, Yang H, Berman HM (2003) The Protein Data Bank and structural genomics. Nucleic Acids Res 31(1):489–491

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Ingwall RT, Scheraga HA, Lotan N, Berger A, Katchalski E (1968) Conformational studies of poly-L-alanine in water. Biopolymers 6:331–368

    Article  CAS  PubMed  Google Scholar 

  29. Lesk AM (1997) CASP2: report on ab initio predictions. Proteins Suppl 1:151–166

    Article  CAS  PubMed  Google Scholar 

  30. Zemla A, Venclovas C, Reinhardt A, Fidelis K, Hubbard TJ (1997) Numerical criteria for the evaluation of ab initio predictions of protein structure. Proteins Suppl 1:140–150

    Article  CAS  PubMed  Google Scholar 

  31. Kolinski A, Rotkiewicz P, Ilkowski B, Skolnick J (1999) A method for the improvement of threading-based protein models. Proteins 37:592–610

    Article  CAS  PubMed  Google Scholar 

  32. Rost B, Fariselli P, Casadio R (1996) Topology prediction for helical transmembrane proteins at 86% accuracy. Protein Sci 5:1704–1718

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Xiang Z (2006) Advances in homology protein structure modeling. Curr Protein Pept Sci 7:217–227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215:403–410

    Article  CAS  PubMed  Google Scholar 

  35. Brünger AT (1992) Free R value: a novel statistical quantity for assessing the accuracy of crystal structures. Nature 355:472–475

    Article  PubMed  Google Scholar 

  36. Ramachandran GN, Ramakrishnan C, Sasisekharan V (1963) Stereochemistry of polypeptide chain configurations. J Mol Biol 7:95–99

    Article  CAS  PubMed  Google Scholar 

  37. Fanelli F, De Benedetti PG (2006) Inactive and active states and supramolecular organization of GPCRs: insights from computational modeling. J Comput Aided Mol Des 20:449–461

    Article  CAS  PubMed  Google Scholar 

  38. Wierenga RK, Borchert TV, Noble ME (1992) Crystallographic binding studies with triosephosphate isomerases: conformational changes induced by substrate and substrate-analogues. FEBS Lett 307:34–39

    Article  CAS  PubMed  Google Scholar 

  39. Sali A, Blundell TL (1993) Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol 234:779–815

    Article  CAS  PubMed  Google Scholar 

  40. De Bondt HL, Rosenblatt J, Jancarik J, Jones HD, Morgan DO, Kim SH (1993) Crystal structure of cyclin-dependent kinase 2. Nature 363:595–602

    Article  PubMed  Google Scholar 

  41. Spring LM, Wander SA, Zangardi M, Bardia A (2019) CDK 4/6 inhibitors in breast cancer: current controversies and future directions. Curr Oncol Rep 21:25

    Article  PubMed  PubMed Central  Google Scholar 

  42. Roskoski R Jr (2019) Cyclin-dependent protein serine/threonine kinase inhibitors as anticancer drugs. Pharmacol Res 139:471–488

    Article  CAS  PubMed  Google Scholar 

  43. Choo JR, Lee SC (2018) CDK4-6 inhibitors in breast cancer: current status and future development. Expert Opin Drug Metab Toxicol 14:1123–1138

    CAS  PubMed  Google Scholar 

  44. Zardavas D, Pondé N, Tryfonidis K (2017) CDK4/6 blockade in breast cancer: current experience and future perspectives. Expert Opin Investig Drugs 26:1357–1372

    Article  CAS  PubMed  Google Scholar 

  45. Chen P, Lee NV, Hu W, Xu M, Ferre RA, Lam H et al (2016) Spectrum and degree of CDK drug interactions predicts clinical performance. Mol Cancer Ther 15:2273–2281

    Article  PubMed  CAS  Google Scholar 

  46. Canduri F, Perez PC, Caceres RA, de Azevedo WF Jr (2008) CDK9 a potential target for drug development. Med Chem 4:210–218

    Article  CAS  PubMed  Google Scholar 

  47. Krystof V, Cankar P, Frysová I, Slouka J, Kontopidis G, Dzubák P et al (2006) 4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. J Med Chem 49:6500–6509

    Article  CAS  PubMed  Google Scholar 

  48. Leopoldino AM, Canduri F, Cabral H, Junqueira M, de Marqui AB, Apponi LH et al (2006) Expression, purification, and circular dichroism analysis of human CDK9. Protein Expr Purif 47:614–620

    Article  CAS  PubMed  Google Scholar 

  49. Canduri F, de Azevedo WF Jr (2005) Structural basis for interaction of inhibitors with cyclin-dependent kinase 2. Curr Comput Aided Drug Des 1:53–64

    Article  CAS  Google Scholar 

  50. Canduri F, Uchoa HB, de Azevedo WF Jr (2004) Molecular models of cyclin-dependent kinase 1 complexed with inhibitors. Biochem Biophys Res Commun 324:661–666

    Article  CAS  PubMed  Google Scholar 

  51. Filgueira de Azevedo W Jr, Gaspar RT, Canduri F, Camera JC Jr, Freitas da Silveira NJ (2002) Molecular model of cyclin-dependent kinase 5 complexed with roscovitine. Biochem Biophys Res Commun 297:1154–1158

    Article  CAS  PubMed  Google Scholar 

  52. de Azevedo WF Jr, Canduri F, da Silveira NJ (2002) Structural basis for inhibition of cyclin-dependent kinase 9 by flavopiridol. Biochem Biophys Res Commun 293:566–571

    Article  PubMed  Google Scholar 

  53. De Azevedo WF Jr, Mueller-Dieckmann HJ, Schulze-Gahmen U, Worland PJ, Sausville E, Kim SH (1996) Structural basis for specificity and potency of a flavonoid inhibitor of human CDK2, a cell cycle kinase. Proc Natl Acad Sci U S A 93:2735–2740

    PubMed  PubMed Central  Google Scholar 

  54. Kim SH, Schulze-Gahmen U, Brandsen J, de Azevedo Júnior WF (1996) Structural basis for chemical inhibition of CDK2. Prog Cell Cycle Res 2:137–145

    Article  CAS  PubMed  Google Scholar 

  55. Cui J, Yang Y, Li H, Leng Y, Qian K, Huang Q et al (2015) MiR-873 regulates era transcriptional activity and tamoxifen resistance via targeting CDK3 in breast cancer cells. Oncogene 34:3895–3907

    Article  CAS  PubMed  Google Scholar 

  56. Perez PC, Caceres RA, Canduri F, de Azevedo WF Jr (2009) Molecular modeling and dynamics simulation of human cyclin-dependent kinase 3 complexed with inhibitors. Comput Biol Med 39:130–140

    Article  CAS  PubMed  Google Scholar 

  57. Benson DA, Cavanaugh M, Clark K, Karsch-Mizrachi I, Lipman DJ, Ostell J et al (2013) GenBank. Nucleic Acids Res 41:36–42

    Article  CAS  Google Scholar 

  58. Edgar RC (2004) MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32:1792–1797

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. De Azevedo WF, Leclerc S, Meijer L, Havlicek L, Strnad M, Kim SH (1997) Inhibition of cyclin-dependent kinases by purine analogues: crystal structure of human cdk2 complexed with roscovitine. Eur J Biochem 243:518–526

    Article  PubMed  Google Scholar 

  60. Thomsen R, Christensen MH (2006) MolDock: a new technique for high-accuracy molecular docking. J Med Chem 49:3315–3321

    Article  CAS  PubMed  Google Scholar 

  61. Abdelmonsef AH, Dulapalli R, Dasari T, Padmarao LS, Mukkera T, Vuruputuri U (2016) Identification of novel antagonists for Rab38 protein by homology modeling and virtual screening. Comb Chem High Throughput Screen 19:875–892

    Article  CAS  PubMed  Google Scholar 

  62. Filgueira de Azevedo W Jr, Canduri F, Simões de Oliveira J, Basso LA, Palma MS, Pereira JH et al (2002) Molecular model of shikimate kinase from Mycobacterium tuberculosis. Biochem Biophys Res Commun 295:142–148

    Article  CAS  PubMed  Google Scholar 

  63. Konno K, Hisada M, Fontana R, Lorenzi CC, Naoki H, Itagaki Y et al (2001) Anoplin, a novel antimicrobial peptide from the venom of the solitary wasp Anoplius samariensis. Biochim Biophys Acta 1550:70–80

    Article  CAS  PubMed  Google Scholar 

  64. Pereira JH, Canduri F, de Oliveira JS, da Silveira NJ, Basso LA, Palma MS et al (2003) Structural bioinformatics study of EPSP synthase from Mycobacterium tuberculosis. Biochem Biophys Res Commun 312:608–614

    Article  CAS  PubMed  Google Scholar 

  65. Rádis-Baptista G, Moreno FB, de Lima Nogueira L, Martins AM, de Oliveira Toyama D, Toyama MH et al (2006) Crotacetin, a novel snake venom C-type lectin homolog of convulxin, exhibits an unpredictable antimicrobial activity. Cell Biochem Biophys 44:412–423

    Article  PubMed  Google Scholar 

  66. Freitas PG, Elias TC, Pinto IA, Costa LT, de Carvalho PVSD, Omote DQ et al (2018) Computational approach to the discovery of phytochemical molecules with therapeutic potential targets to the PKCZ protein. Lett Drug Des Discov 15:488–499

    Article  CAS  Google Scholar 

  67. Uchôa HB, Jorge GE, Freitas Da Silveira NJ, Camera JC Jr, Canduri F, De Azevedo WF Jr (2004) Parmodel: a web server for automated comparative modeling of proteins. Biochem Biophys Res Commun 325:1481–1486

    Article  CAS  PubMed  Google Scholar 

  68. Arcuri HA, Borges JC, Fonseca IO, Pereira JH, Neto JR, Basso LA et al (2008) Structural studies of shikimate 5-dehydrogenase from Mycobacterium tuberculosis. Proteins 72:720–730

    Article  CAS  PubMed  Google Scholar 

  69. Arcuri HA, Apponi LH, Valentini SR, Durigon EL, de Azevedo WF Jr, Fossey MA et al (2008) Expression and purification of human respiratory syncytial virus recombinant fusion protein. Protein Expr Purif 62:146–152

    Article  CAS  PubMed  Google Scholar 

  70. de Azevedo WF Jr (2010) Structure-based virtual screening. Curr Drug Targets 11:261–263

    Article  PubMed  Google Scholar 

  71. de Ávila MB, Bitencourt-Ferreira G, de Azevedo WF Jr (2018) Structural basis for inhibition of enoyl-[acyl carrier protein] reductase (InhA) from Mycobacterium tuberculosis. Curr Med Chem. https://doi.org/10.2174/0929867326666181203125229

  72. Volkart PA, Bitencourt-Ferreira G, Souto AA, de Azevedo WF (2019) Cyclin-dependent kinase 2 in cellular senescence and cancer. A structural and functional review. Curr Drug Targets 20:716–726. https://doi.org/10.2174/1389450120666181204165344

    Article  CAS  PubMed  Google Scholar 

  73. Canduri F, Fadel V, Basso LA, Palma MS, Santos DS, de Azevedo WF Jr (2005) New catalytic mechanism for human purine nucleoside phosphorylase. Biochem Biophys Res Commun 327:646–649

    Article  CAS  PubMed  Google Scholar 

  74. Canduri F, Teodoro LG, Fadel V, Lorenzi CC, Hial V, Gomes RA et al (2001) Structure of human uropepsin at 2.45 A resolution. Acta Crystallogr D Biol Crystallogr 57:1560–1570

    Article  CAS  PubMed  Google Scholar 

  75. de Azevedo WF Jr, Dias R (2008) Experimental approaches to evaluate the thermodynamics of protein-drug interactions. Curr Drug Targets 9:1071–1076

    Article  PubMed  Google Scholar 

  76. Delatorre P, Rocha BA, Souza EP, Oliveira TM, Bezerra GA, Moreno FB et al (2007) Structure of a lectin from Canavalia gladiata seeds: new structural insights for old molecules. BMC Struct Biol 7:52

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. de Azevedo WF Jr, Canduri F, dos Santos DM, Pereira JH, Bertacine Dias MV, Silva RG et al (2003) Crystal structure of human PNP complexed with guanine. Biochem Biophys Res Commun 312:767–772

    Article  CAS  PubMed  Google Scholar 

  78. Canduri F, Perez PC, Caceres RA, de Azevedo WF Jr (2007) Protein kinases as targets for antiparasitic chemotherapy drugs. Curr Drug Targets 8:389–398

    Article  CAS  PubMed  Google Scholar 

  79. Dias MV, Borges JC, Ely F, Pereira JH, Canduri F, Ramos CH et al (2006) Structure of chorismate synthase from Mycobacterium tuberculosis. J Struct Biol 154:130–143

    Article  CAS  PubMed  Google Scholar 

  80. Dias MV, Ely F, Palma MS, de Azevedo WF Jr, Basso LA, Santos DS (2007) Chorismate synthase: an attractive target for drug development against orphan diseases. Curr Drug Targets 8:437–444

    Article  CAS  PubMed  Google Scholar 

  81. Silva RG, Pereira JH, Canduri F, de Azevedo WF Jr, Basso LA, Santos DS (2005) Kinetics and crystal structure of human purine nucleoside phosphorylase in complex with 7-methyl-6-thio-guanosine. Arch Biochem Biophys 442:49–58

    Article  CAS  PubMed  Google Scholar 

  82. Timmers LF, Caceres RA, Vivan AL, Gava LM, Dias R, Ducati RG et al (2008) Structural studies of human purine nucleoside phosphorylase: towards a new specific empirical scoring function. Arch Biochem Biophys 479:28–38

    Article  CAS  PubMed  Google Scholar 

  83. de Azevedo WF Jr (2011) Molecular dynamics simulations of protein targets identified in Mycobacterium tuberculosis. Curr Med Chem 18:1353–1366

    Article  PubMed  Google Scholar 

  84. de Azevedo WF Jr (2011) Protein targets for development of drugs against Mycobacterium tuberculosis. Curr Med Chem 18:1255–1257

    Article  PubMed  Google Scholar 

  85. Caceres RA, Saraiva Timmers LF, Dias R, Basso LA, Santos DS, de Azevedo WF Jr (2008) Molecular modeling and dynamics simulations of PNP from Streptococcus agalactiae. Bioorg Med Chem 16:4984–4993

    Article  CAS  PubMed  Google Scholar 

  86. Dias MV, Faím LM, Vasconcelos IB, de Oliveira JS, Basso LA, Santos DS et al (2007) Effects of the magnesium and chloride ions and shikimate on the structure of shikimate kinase from Mycobacterium tuberculosis. Acta Crystallogr Sect F Struct Biol Cryst Commun 63:1–6

    Article  CAS  PubMed  Google Scholar 

  87. de Azevedo WF Jr, Ward RJ, Canduri F, Soares A, Giglio JR, Arni RK (1998) Crystal structure of piratoxin-I: a calcium-independent, myotoxic phospholipase A2-homologue from Bothrops pirajai venom. Toxicon 36:1395–1406

    Article  PubMed  Google Scholar 

  88. Dias R, Timmers LF, Caceres RA, de Azevedo WF Jr (2008) Evaluation of molecular docking using polynomial empirical scoring functions. Curr Drug Targets 9:1062–1070

    Article  CAS  PubMed  Google Scholar 

  89. da Silveira NJ, Uchôa HB, Canduri F, Pereira JH, Camera JC Jr, Basso LA et al (2004) Structural bioinformatics study of PNP from Schistosoma mansoni. Biochem Biophys Res Commun 322:100–104

    PubMed  Google Scholar 

  90. de Azevedo WF Jr, Dias R (2008) Evaluation of ligand-binding affinity using polynomial empirical scoring functions. Bioorg Med Chem 16:9378–9382

    Article  PubMed  CAS  Google Scholar 

  91. Bezerra GA, Oliveira TM, Moreno FB, de Souza EP, da Rocha BA, Benevides RG et al (2007) Structural analysis of Canavalia maritima and Canavalia gladiata lectins complexed with different dimannosides: new insights into the understanding of the structure-biological activity relationship in legume lectins. J Struct Biol 160:168–176

    Article  CAS  PubMed  Google Scholar 

  92. Canduri F, Fadel V, Dias MV, Basso LA, Palma MS, Santos DS et al (2005) Crystal structure of human PNP complexed with hypoxanthine and sulfate ion. Biochem Biophys Res Commun 326:335–338

    CAS  PubMed  Google Scholar 

  93. Timmers LF, Pauli I, Caceres RA, de Azevedo WF Jr (2008) Drug-binding databases. Curr Drug Targets 9:1092–1099

    Article  CAS  PubMed  Google Scholar 

  94. Delatorre P, Rocha BA, Gadelha CA, Santi-Gadelha T, Cajazeiras JB, Souza EP et al (2006) Crystal structure of a lectin from Canavalia maritima (ConM) in complex with trehalose and maltose reveals relevant mutation in ConA-like lectins. J Struct Biol 154:280–286

    Article  CAS  PubMed  Google Scholar 

  95. Nolasco DO, Canduri F, Pereira JH, Cortinóz JR, Palma MS, Oliveira JS et al (2004) Crystallographic structure of PNP from Mycobacterium tuberculosis at 1.9A resolution. Biochem Biophys Res Commun 324:789–794

    Article  CAS  PubMed  Google Scholar 

  96. Arcuri HA, Canduri F, Pereira JH, da Silveira NJ, Camera Júnior JC, de Oliveira JS et al (2004) Molecular models for shikimate pathway enzymes of Xylella fastidiosa. Biochem Biophys Res Commun 320:979–991

    Article  CAS  PubMed  Google Scholar 

  97. Soares MB, Silva CV, Bastos TM, Guimarães ET, Figueira CP, Smirlis D et al (2012) Anti-Trypanosoma cruzi activity of nicotinamide. Acta Trop 12:224–229

    Article  CAS  Google Scholar 

  98. Manhani KK, Arcuri HA, da Silveira NJ, Uchôa HB, de Azevedo WF Jr, Canduri F (2005) Molecular models of protein kinase 6 from Plasmodium falciparum. J Mol Model 12:42–48

    Article  CAS  PubMed  Google Scholar 

  99. Marques MR, Vaso A, Neto JR, Fossey MA, Oliveira JS, Basso LA et al (2008) Dynamics of glyphosate-induced conformational changes of Mycobacterium tuberculosis 5-enolpyruvylshikimate-3-phosphate synthase (EC 2.5.1.19) determined by hydrogen-deuterium exchange and electrospray mass spectrometry. Biochemistry 47:7509–7522

    Article  CAS  PubMed  Google Scholar 

  100. Cavada BS, Moreno FB, da Rocha BA, de Azevedo WF Jr, Castellón RE, Goersch GV et al (2006) cDNA cloning and 1.75 A crystal structure determination of PPL2, an endochitinase and N-acetylglucosamine-binding hemagglutinin from Parkia platycephala seeds. FEBS J 273:3962–3974

    Article  CAS  PubMed  Google Scholar 

  101. Moreno FB, de Oliveira TM, Martil DE, Viçoti MM, Bezerra GA, Abrego JR et al (2008) Identification of a new quaternary association for legume lectins. J Struct Biol 161:133–143

    Article  CAS  PubMed  Google Scholar 

  102. Xavier MM, Heck GS, de Avila MB, Levin NM, Pintro VO, Carvalho NL et al (2016) SAnDReS a computational tool for statistical analysis of docking results and development of scoring functions. Comb Chem High Throughput Screen 19:801–812

    Article  CAS  PubMed  Google Scholar 

  103. de Ávila MB, Xavier MM, Pintro VO, de Azevedo WF (2017) Supervised machine learning techniques to predict binding affinity. A study for cyclin-dependent kinase 2. Biochem Biophys Res Commun 494:305–310

    Article  PubMed  CAS  Google Scholar 

  104. Bitencourt-Ferreira G, de Azevedo WF Jr (2018) Development of a machine-learning model to predict Gibbs free energy of binding for protein-ligand complexes. Biophys Chem 240:63–69

    Article  CAS  PubMed  Google Scholar 

  105. Levin NMB, Pintro VO, Bitencourt-Ferreira G, Mattos BB, Silvério AC, de Azevedo WF Jr (2018) Development of CDK-targeted scoring functions for prediction of binding affinity. Biophys Chem 235:1–8

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from CNPq (Brazil) (308883/2014-4). This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior—Brasil (CAPES)—Finance Code 001. GBF acknowledges support from PUCRS/BPA fellowship. WFA is a senior researcher for CNPq (Brazil) (Process Numbers: 308883/2014-4 and 309029/2018-0).

Author information

Authors and Affiliations

  1. Escola de Ciências da Saúde, Pontifícia Universidade Católica do Rio Grande do Sul—PUCRS, Porto Alegre, RS, Brazil

    Gabriela Bitencourt-Ferreira & Walter Filgueira de Azevedo Jr.

Authors
  1. Gabriela Bitencourt-Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Walter Filgueira de Azevedo Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Walter Filgueira de Azevedo Jr. .

Editor information

Editors and Affiliations

  1. Escola de Ciências da Saúde, Pontifícia Universidade Católica do Rio Grande do Sul—PUCRS, Porto Alegre, Rio Grande do Sul, Brazil

    Walter Filgueira de Azevedo Jr.

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Bitencourt-Ferreira, G., de Azevedo, W.F. (2019). Homology Modeling of Protein Targets with MODELLER. In: de Azevedo Jr., W. (eds) Docking Screens for Drug Discovery. Methods in Molecular Biology, vol 2053. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9752-7_15

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-9752-7_15

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9751-0

  • Online ISBN: 978-1-4939-9752-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation