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Pharmacophore modeling improves virtual screening for novel peroxisome proliferator-activated receptor-gamma ligands

Journal of Computer-Aided Molecular Design volume 29, pages 421–439 (2015)Cite this article

Abstract

Peroxisome proliferator-activated receptor-gamma (PPARγ) is a nuclear hormone receptor involved in regulating various metabolic and immune processes. The PPAR family of receptors possesses a large binding cavity that imparts promiscuity of ligand binding not common to other nuclear receptors. This feature increases the challenge of using computational methods to identify PPAR ligands that will dock favorably into a structural model. Utilizing both ligand- and structure-based pharmacophore methods, we sought to improve agonist prediction by grouping ligands according to pharmacophore features, and pairing models derived from these features with receptor structures for docking. For 22 of the 33 receptor structures evaluated we observed an increase in true positive rate (TPR) when screening was restricted to compounds sharing molecular features found in rosiglitazone. A combination of structure models used for docking resulted in a higher TPR (40 %) when compared to docking with a single structure model (<20 %). Prediction was also improved when specific protein–ligand interactions between the docked ligands and structure models were given greater weight than the calculated free energy of binding. A large-scale screen of compounds using a marketed drug database verified the predictive ability of the selected structure models. This study highlights the steps necessary to improve screening for PPARγ ligands using multiple structure models, ligand-based pharmacophore data, evaluation of protein–ligand interactions, and comparison of docking datasets. The unique combination of methods presented here holds potential for more efficient screening of compounds with unknown affinity for PPARγ that could serve as candidates for therapeutic development.

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References

  1. Tontonoz P, Spiegelman BM (2008) Annu Rev Biochem 77:289

    CAS  Article  Google Scholar 

  2. Gampe RT, Montana VG, Lambert MH, Miller AB, Bledsoe RK, Milburn MV, Kliewer SA, Willson TM, Xu HE (2000) Mol Cell 5:545

    CAS  Article  Google Scholar 

  3. Bassaganya-Riera J, Guri A, King J, Hontecillas R (2005) Curr Nutr Food Sci 1:179

    CAS  Article  Google Scholar 

  4. Guri AJ, Hontecillas R, Bassaganya-Riera J (2006) Clin Nutr 25:871

    CAS  Article  Google Scholar 

  5. Rosen ED, Hsu C-H, Wang X, Sakai S, Freeman MW, Gonzalez FJ, Spiegelman BM (2002) Genes Dev 16(1):22

    CAS  Article  Google Scholar 

  6. Martin H (2009) Mutat Res/Fundam Mol Mech Mutagen 669:1

    CAS  Article  Google Scholar 

  7. Shao D, Rangwala S, Bailey S, Krakow S, Reginato M, Lazar M (1998) Nature 396(6709):377

    CAS  Article  Google Scholar 

  8. Wahli W (2008) J Intern Med 263:613

    CAS  Article  Google Scholar 

  9. Straus DS, Glass CK (2007) Trends Immunol 28(12):551

    CAS  Article  Google Scholar 

  10. Bassaganya-Riera J, Ferrer G, Casagran O, Sanchez S, de Horna A, Duran E, Orpi M, Guri AJ, Hontecillas R (2009) e-SPEN Eur e-J Clin Nutr Metab 4:e90

    Article  Google Scholar 

  11. Bassaganya-Riera J, Mikyak S, Guri AJ, Hontecillas R (2009) Cell Immunol 258:138

    CAS  Article  Google Scholar 

  12. Lewis SN, Bassaganya-Riera J, Bevan DR (2010) PPAR Res 2010. doi:10.1155/2010/861238

  13. Huang TH-W, Teoh AW, Lin B-L, Lin DS-H, Roufogalis B (2009) Pharmacol Res 60:195

    CAS  Article  Google Scholar 

  14. Itoh T, Fairall L, Amin K, Inaba Y, Szanto A, Balint BL, Nagy L, Yamamoto K, Schwabe JWR (2008) Nat Struct Mol Biol 15(9):924

    CAS  Article  Google Scholar 

  15. Pochetti G, Godio C, Mitro N, Caruso D, Galmozzi A, Scurati S, Loiodice F, Fracchiolla G, Tortorella P, Laghezza A, Lavecchia A, Novellino E, Mazza F, Crestani M (2007) J Biol Chem 282(23):17314

    CAS  Article  Google Scholar 

  16. Nolte RT, Wisely GB, Westin S, Cobb JE, Lambert MH, Kurokawa R, Rosenfeld MG, Willson TM, Glass CK, Milburn MV (1998) Nature 395:137

    CAS  Article  Google Scholar 

  17. Casimiro-Garcia A, Bigge CF, Davis JA, Padalino T, Pulaski J, Ohren JF, McConnell P, Kane CD, Royer LJ, Stevens KA, Auerbach BJ, Collard WT, McGregor C, Fakhoury SA, Schaum RP, Zhou H (2008) Bioorg Med Chem 16(9):4883

    CAS  Article  Google Scholar 

  18. Farce A, Renault N, Chavatte P (2009) Curr Med Chem 16(14):1768

    CAS  Article  Google Scholar 

  19. Higgins LS, DePaoli AM (2010) Am J Clin Nutr 91:267S

    CAS  Article  Google Scholar 

  20. Shearer B, Billin A (2007) Biochim Biophys Acta 1771(8):1082

    CAS  Article  Google Scholar 

  21. Gelman L, Feige JN, Desvergne B (2007) Biochim Biophys Acta 1771(8):1094

    CAS  Article  Google Scholar 

  22. Kallenberger BC, Love JD, Krishna V, Chatterjee K, Schwabe JWR (2003) Nature 10(2):136

    CAS  Google Scholar 

  23. Rosen ED, Spiegelman BM (2001) J Biol Chem 276(41):37731

    CAS  Article  Google Scholar 

  24. Xu HE, Stanley TB, Montana VG, Lambert MH, Shearer BG, Cobb JE, McKee DD, Galardi CM, Plunket KD, Nolte RT, Parks DJ, Moore JT, Kliewer SA, Willson TM, Stimmel JB (2002) Nature 415:813

    CAS  Article  Google Scholar 

  25. DeGrazia MJ, Thompson J, Vanden Heuvel JP, Peterson BR (2003) Bioorg Med Chem 11:4325

    CAS  Article  Google Scholar 

  26. Wu B, Gao J, Wang M-W (2005) Acta Pharmacol Sin 26(3):339

    CAS  Article  Google Scholar 

  27. Klebe G (2006) Drug Discov Today 11(13–14):580

    CAS  Article  Google Scholar 

  28. Brozell SR, Mukherjee S, Balius TE, Roe DR, Case DA, Rizzo RC (2012) J Comput Aided Mol Des 26(6):749

    CAS  Article  Google Scholar 

  29. Irwin J, Shoichet B, Mysinger M, Huang N, Colizzi F, Wassam P, Cao Y (2009) J Med Chem 52(18):5712

    CAS  Article  Google Scholar 

  30. Huang N, Shoichet BK, Irwin JJ (2006) J Med Chem 49(23):6789

    CAS  Article  Google Scholar 

  31. Mysinger MM, Carchia M, Irwin JJ, Shoichet BK (2013) J Med Chem 55:6582

    Article  Google Scholar 

  32. Zhang X, Wong SE, Lightstone FC (2013) J Comput Chem 34:915

    CAS  Article  Google Scholar 

  33. Cavasotto CN, Abagyan A (2004) J Mol Biol 337:209

    CAS  Article  Google Scholar 

  34. Lyne PD (2002) Drug Discov Today 7(20):1047

    CAS  Article  Google Scholar 

  35. Stahura FL, Bajorath J (2005) Curr Pharm Des 11:1189

    CAS  Article  Google Scholar 

  36. Maltarollo V, Honorio K (2012) Chem Biol Drug Des 80(4):533

    CAS  Article  Google Scholar 

  37. Schneidman-Duhovny D, Dror O, Inbar Y, Nussinov R, Wolfson H (2008) Nucleic Acids Res 36:W223

    CAS  Article  Google Scholar 

  38. Yang S-Y (2010) Drug Discov Today 15(11–12):444

    CAS  Article  Google Scholar 

  39. Berman HM, Battistuz T, Bhat TN, Bluhm W, Bourne PE, Burkhardt K, Feng Z, Gilliland GL, Iype L, Jain S, Fagan P, Marvin J, Padilla D, Ravichandran V, Thanki N, Weissig H, Westbrook JD, Zardecki C (2002) Acta Crystallogr D Biol Crystallogr D58:899

    CAS  Article  Google Scholar 

  40. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyolov IN, Bourne PE (2000) Nucleic Acids Res 28:235

    CAS  Article  Google Scholar 

  41. Harris R, Olson AJ, Goodsell DS (2007) Proteins Struct Funct Bioinform 70:1506

  42. Pettersen E, Goddard T, Huang C, Couch G, Greenblatt D, Meng E, Ferrin T (2004) J Comput Chem 25(13):1605

    CAS  Article  Google Scholar 

  43. Zoete V, Grosdidier A, Michielin O (2007) Biochim Biophys Acta 1771:915

    CAS  Article  Google Scholar 

  44. Markt P, Schuster D, Kirchmair J, Laggner C, Langer T (2007) J Comput Aided Mol Des 21:575

    CAS  Article  Google Scholar 

  45. Hopkins CR, O’Neil SV, Laufersweiler MC, Wang Y, Pokross M, Mekel M, Evdokimov A, Walter R, Kontoyianni M, Petrey ME, Sabatakos G, Roesgen JT, Richardson E, Demuth TP Jr (2006) Bioorg Med Chem Lett 16(21):5659

    CAS  Article  Google Scholar 

  46. Chandra V, Huang P, Hamuro Y, Raghuram S, Wang Y, Burris TP, Rastinejad F (2008) Nature 456:350

    Article  Google Scholar 

  47. Xu HE, Lambert MH, Montana VG, Plunket KD, Moore LB, Collins JL, Oplinger JA, Kliewer SA, Gampe RT Jr, McKee DD, Moore JT, Willson TM (2001) Proc Natl Acad Sci 98(24):13919

    CAS  Article  Google Scholar 

  48. Haffner C, Lenhard J, Miller A, McDougald D, Dwornik K, Ittoop O, Gampe R Jr, Xu H, Blanchard S, Montana V, Consler T, Bledsoe R, Ayscue A, Croom D (2004) J Med Chem 47:2010

    CAS  Article  Google Scholar 

  49. Li Y, Choi M, Suino K, Kovach A, Daugherty J, Kliewer SA, Xu HE (2005) Proc Natl Acad Sci 102(27):9505

    CAS  Article  Google Scholar 

  50. Mahindroo N, Huang CF, Peng YH, Wang CC, Liao CC, Lien TW, Chittimalla SK, Huang WJ, Chai CH, Prakash E, Chen CP, Hsu TA, Peng CH, Lu IL, Lee LH, Chang YW, Chen WC, Chou YC, Chen CT, Goparaju CM, Chen YS, Lan SJ, Yu MC, Chen X, Chao YS, Wu SY, Hsieh HP (2005) J Med Chem 48(26):8194

    CAS  Article  Google Scholar 

  51. Trump R, Cobb J, Shearer B, Lambert M, Nolte R, Wilson TM, Buckholz R, Zhao S, Leesnitzer L, Iannone M, Pearce K, Billin A, Hoekstra W (2007) Science Direct 17:3916

  52. Bruning JB, Chalmers MJ, Prasad S, Busby SA, Kamenechka TM, He Y, Nettles KW, Griffin PR (2007) Structure 15:1258

    CAS  Article  Google Scholar 

  53. Montanari R, Saccoccia F, Scotti E, Crestani M, Godio C, Gilardi F, Loiodice F, Fracchiolla G, Laghezza A, Tortorella P, Lavecchia A, Novellino E, Mazza F, Aschi M, Pochetti G (2008) J Med Chem 51(24):7768

    CAS  Article  Google Scholar 

  54. Li Y, Kovach A, Suino-Powell K, Martynowski D, Xu HE (2008) J Biol Chem 283(27):19132

    CAS  Article  Google Scholar 

  55. Mueller J, Schupp M, Unger T, Kintscher U, Heinemann U (2011) No publication

  56. Waku T, Shiraki T, Oyama T, Fujimoto Y, Maebara K, Kamiya N, Jingami H, Morikawa K (2009) J Mol Biol 385(1):188

    CAS  Article  Google Scholar 

  57. Oyama T, Toyota K, Waku T, Hirakawa Y, Nagasawa N, Kasuga J, Hashimoto Y, Miyashi H, Morikawa K (2009) Acta Crystallogr D Biol Crystallogr 65:786

    CAS  Article  Google Scholar 

  58. Waku T, Shiraki T, Oyama T, Maebara K, Nakamori R, Morikawa K (2010) EMBO J 29:3395

    CAS  Article  Google Scholar 

  59. Ohashi M, Oyama T, Nakagome I, Satoh M, Nishio Y, Nobusada H, Hirono S, Morikawa K, Hashimoto Y, Miyachi H (2011) J Med Chem 54:331

    CAS  Article  Google Scholar 

  60. Tomioka D, Hashimoto H, Sato M, Shimizu T (2011) No publication

  61. Artis DR, Lin JJ, Wang W, Mehra U, Perreault M, Erbe D, Krupka HI, England BP, Arnold J, Plotnikov AN, Marimuthu A, Nguyen H, Will S, Signaevsky M, Kral J, Cantwell J, Settachatgull C, Yan DS, Fong D, Oh A, Shi S, Womack P, Powell B, Habets G, West BL, Zhang KYJ, Milburn MV, Vlasuk GP, Hirth KP, Nolop K, Bollag G, Ibrahim PN, Tobin JF (2009) PNAS 106(1):262

    CAS  Article  Google Scholar 

  62. Lin C, Peng Y, Coumar M, Chittimalla SK, Liao CC, Lyn P, Huang C, Lien TW, Lin W, Hsu J, Cheng J, Chen X, Wu J, Chao YS, Lee H, Juo C, Wu S, Hsieh HP (2009) J Med Chem 52:2618

    CAS  Article  Google Scholar 

  63. Connors RV, Wang Z, Harrison M, Zhang A, Wanska M, Hiscock S, Fox B, Dore M, Labelle M, Sudom A, Johnstone S, Liu J, Walker NPC, Chai A, Siegler K, Li Y, Coward P (2009) Bioorg Med Chem Lett 19(13):3550

    CAS  Article  Google Scholar 

  64. Fracchiolla G, Laghezza A, Piemontese L, Tortorella P, Mazza F, Montanari R, Pochetti G, Lavecchia A, Novellino E, Pierno S, Camerino DC, Loiodice F (2009) J Med Chem 52(20):6382

    CAS  Article  Google Scholar 

  65. Peng YH, Coumar M, Leou J, Wu J, Shiao H, Lin C, Lyu P, Hsieh HP, Wu SY (2011) No publication

  66. Ostberg T, Svensson S, Selen G, Uppenberg J, Thor M, Sundbom M, Sydow-Backman M, Gustavsson A, Jendeberg L (2004) J Biol Chem 279:41124

    Article  Google Scholar 

  67. Burgermeister E, Schnoebelen A, Flament A, Benz J, Stihle M, Gsell B, Rufer A, Ruf A, Kuhn B, Maerki HP, Mizrahi J, Sebokova E, Niesor E, Meyer M (2006) Mol Endocrinol 20(4):809

    CAS  Article  Google Scholar 

  68. Lu I-L, Huang C-F, Peng Y-H, Lin Y-T, Hsieh H-P, Chen C-T, Lien T-W, Lee H-J, Mahindroo N, Prakash E, Yueh A, Chen H-Y, Goparaju CMV, Chen X, Liao C-C, Chao Y-S, Jsu JT-A, Wu S-Y (2006) J Med Chem 49(9):2703

    CAS  Article  Google Scholar 

  69. Ambrosio AL, Dias SM, Polikarpov I, Zurier RB, Burstein SH, Garratt RC (2007) J Biol Chem 282(25):18625

    CAS  Article  Google Scholar 

  70. Einstein M, Akiyama TE, Castriota GA, Wang CF, McKeever B, Mosley RT, Becker JW, Moller DE, Meinke PT, Wood HB, Berger JP (2008) Mol Pharmacol 73(1):62

    CAS  Article  Google Scholar 

  71. Fracchiolla G, Laghezza A, Piemontese L, Parente M, Lavecchia A, Pochetti G, Montanari R, Di Giovanni C, Carbonara G, Tortorella P, Novellino E, Loiodice F (2012) Bioorg Med Chem 20:2141

  72. Oberfield J, Collins J, Holmes C, Goreham D, Cooper J, Cobb J, Lenhard J, Hull-Ryde E, Mohr C, Blanchard S, Parks D, Moore L, Lehmann J, Plunket K, Miller A, Milburn M, Kliewer S, Willson T (1999) Proc Natl Acad Sci USA 96:6102

    CAS  Article  Google Scholar 

  73. Wakabayashi K, Hayashi S, Matsui Y, Matsumoto T, Furukawa A, Kuroha M, Tanaka N, Inaba T, Kanda S, Tanaka J, Okuyama R, Wakimoto S, Ogata T, Araki K, Ohsumi J (2011) Biol Pharm Bull 34(7):1094

    CAS  Article  Google Scholar 

  74. Motani A, Wang Z, Weiszmann J, McGee L, Lee G, Liu Q, Staunton J, Fang Z, Fuentes H, Lindstrom M, Liu J, Biermann D, Jaen J, Walker N, Learned R, Chen J, Li Y (2009) J Mol Biol 386:1301

    CAS  Article  Google Scholar 

  75. Li Y, Wang Z, Furukawa N, Escaron P, Weiszmann J, Lee G, Lindstrom M, Liu J, Liu X, Xu H, Plotnikova O, Prasad V, Walker N, Learned R, Chen J (2008) J Biol Chem 283(14):9168

    CAS  Article  Google Scholar 

  76. Furukawa A, Arita T, Satoh S, Wakabayashi K, Hayashi S, Matsui Y, Araki K, Kuroha M, Ohsumi J (2010) Bioorg Med Chem Lett 20(7):2095

    CAS  Article  Google Scholar 

  77. Riu A, Grimaldi M, le Maire A, Bey G, Phillips K, Boulahtouf A, Perdu E, Zalko D, Bourguet W, Balaguer P (2011) Environ Health Perspect 119(9):1227

    CAS  Article  Google Scholar 

  78. Riu A, le Maire A, Grimaldi M, Audebert M, Hillenweck A, Bourguet W, Balaguer P, Zalko D (2011) Toxicol Sci 122(2):372

    CAS  Article  Google Scholar 

  79. Inbar Y, Schneidman-Duhovny D, Dror O, Nussinov R, Wolfson H (2007) In Proc of RECOMB 3692 of Lecture Notes in Computer Science:423

  80. Molecular Operating Environment. 2012.10. 1010 Sherbooke St. West, Suite #910, Montreal, QC, Canada, H3A 2R7: Chemical Computing Group Inc.; 2012

  81. Trott O, Olson AJ (2010) J Comput Chem 31(2):455

    CAS  Google Scholar 

  82. Lewis SN, Brannan L, Guri AJ, Lu P, Hontecillas R, Bassaganya-Riera J, Bevan DR (2011) PLoS ONE 6(8):e24031

    CAS  Article  Google Scholar 

  83. Schwartz RL, Phoenix T, Foy BD. Learning Perl. 5th ed ed: O’Reilly Media, Inc., 2008

  84. Kellenberger E, Rodrigo J, Muller P, Rognan D (2004) Proteins 57:255

  85. Triballeau N, Acher F, Brabet I, Pin J-P, Bertrand H-O (2005) J Med Chem 48(7):2534

    CAS  Article  Google Scholar 

  86. Irwin JJ, Shoichet BK (2005) J Chem Inf Model 45:177

    CAS  Article  Google Scholar 

  87. Sushko I, Salmina E, Potemkin V, Poda G, Tetko I (2012) J Chem Inf Model 52(8):2310

    CAS  Article  Google Scholar 

  88. Kazius J, McGuire R, Bursi R (2005) J Med Chem 48(1):312

    CAS  Article  Google Scholar 

  89. Oprea T (2000) J Comput Aided Mol Des 14(3):251

    CAS  Article  Google Scholar 

  90. Tanrikulu Y, Rau O, Schwarz O, Proschak E, Siems K, Muller-Kuhrt L, Schubert-Zsilavecz M, Schneider G (2009) ChemBioChem 10:75

    CAS  Article  Google Scholar 

  91. Willson TM, Brown PJ, Sternbach DD, Henke BR (2000) J Med Chem 43(4):527

    CAS  Article  Google Scholar 

  92. Young PW, Buckle DR, Cantello BCC, Chapman H, Clapham JC, Coyle PJ, Haigh D, Hindley RM, Holder JC, Kallender H, Latter AJ, Lawrie KWM, Mossakowska D, Murphy GJ, Cox LR, Smith SA (1998) J Pharmacol Exp Ther 284(2):751

    CAS  Google Scholar 

  93. Kitchen DB, Decornez H, Furr JR, Bajorath J (2004) Nat Rev Drug Discov 3:935

    CAS  Article  Google Scholar 

  94. Lehmann J, Lenhard J, Oliver B, Ringold G, Kliewer S (1997) J Biol Chem 272(6):3406

    CAS  Article  Google Scholar 

  95. Wiggins J, Rajapakse R (2009) Expert Opin Drug Metab Toxicol 5(10):1279

    CAS  Article  Google Scholar 

  96. Lewis JD, Lichtenstein GR, Deren JJ, Sands BE, Hanauer SB, Katz JA, Lashner B, Present DH, Chuai S, Ellenburg JH, Nessel L, Wu GD (2008) Gastroenterology 134:688

    CAS  Article  Google Scholar 

  97. Patil SA, Moss AC (2008) Expert Rev Gastroenterol Hepatol 2(2):177

    CAS  Article  Google Scholar 

  98. Guasch L, Sala E, Castell-Auví A, Cedó L, Liedl KR, Wolber G, Muehlbacher M, Mulero M, Pinent M, Ardévol A, Valls C, Pujadas G, Garcia-Vallvé S (2012) PLoS ONE 7(11):e50816

    CAS  Article  Google Scholar 

  99. Paliwal S, Yadav D, Yadav R, Paliwal S (2011) Med Chem Res 20:656

    CAS  Article  Google Scholar 

  100. Petersen R, Christensen K, Assimopoulou A, Fretté X, Papageorgiou V, Kristiansen K, Kouskoumvekaki I (2011) J Comput Aided Mol Des 25(2):107

    CAS  Article  Google Scholar 

  101. Sohn Y-S, Lee Y, Park C, Hwang S, Kim S, Baek A, Son M, Suh J-K, Kim H-H, Lee KW (2011) Bull Korean Chem Soc 32(1):201

    CAS  Article  Google Scholar 

  102. Bassaganya-Riera J, Hontecillas R (2006) Clin Nutr 25:454

    CAS  Article  Google Scholar 

  103. Lakatos P (2006) World J Gastroenterol 12(38):6102

    Google Scholar 

  104. Azoulay L, Yin H, Filion KB, Assayag J, Majdan A, Pollak MN, Suissa S (2012) Br Med J 344:e3645

    Article  Google Scholar 

  105. Lewis JD, Ferrara A, Peng T, Hedderson M, Bilker WB, Quesenberry CPJ, Vaughn DJ, Nessel L, Selby J, Strom BL (2011) Diabetes Care 34(4):916

    CAS  Article  Google Scholar 

  106. Cohen J (2006) Diabetologia 49(6):1454

    CAS  Article  Google Scholar 

  107. Henney JE (2000) J Am Med Assoc 283(17):2228

    Article  Google Scholar 

  108. Nissen SE, Wolski K (2010) Arch Intern Med 170(14):1191

    CAS  Article  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Lera Brannan for her initial efforts with identifying ligand-based pharmacophore screening methods to use for this study. The authors would also like to thank Dr. David Goodsell for his help with visualization techniques for the AutoLigand data. The authors acknowledge Advanced Research Computing at Virginia Tech for providing computational resources and technical support, which contributed to the results reported within this paper. http://www.arc.vt.edu. Funding was provided by the National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) (Grant Number 1F31DK091186-01A1).

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Affiliations

  1. Genetics, Bioinformatics, and Computational Biology Program, Virginia Tech, Blacksburg, VA, USA

    Stephanie N. Lewis, Raquel Hontecillas, Josep Bassaganya-Riera & David R. Bevan

  2. Department of Biochemistry, Virginia Tech, Blacksburg, VA, USA

    Stephanie N. Lewis & David R. Bevan

  3. Virginia College of Osteopathic Medicine, Virginia Tech, Blacksburg, VA, USA

    Zulma Garcia

  4. Nutritional Immunology and Molecular Medicine Laboratory, Center for Modeling Immunity to Enteric Pathogens, Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, VA, USA

    Stephanie N. Lewis, Raquel Hontecillas & Josep Bassaganya-Riera

  5. Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA

    Josep Bassaganya-Riera

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  1. Stephanie N. Lewis
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  2. Zulma Garcia
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  3. Raquel Hontecillas
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  4. Josep Bassaganya-Riera
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  5. David R. Bevan
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Correspondence to David R. Bevan.

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Lewis, S.N., Garcia, Z., Hontecillas, R. et al. Pharmacophore modeling improves virtual screening for novel peroxisome proliferator-activated receptor-gamma ligands. J Comput Aided Mol Des 29, 421–439 (2015). https://doi.org/10.1007/s10822-015-9831-x

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  • DOI: https://doi.org/10.1007/s10822-015-9831-x

Keywords

  • Virtual screening
  • Computational molecular docking
  • PPARγ
  • Pharmacophore modeling
  • Drug discovery and design