Table of Contents Author Guidelines Submit a Manuscript
Journal of Tropical Medicine
Volume 2011, Article ID 657483, 15 pages
http://dx.doi.org/10.1155/2011/657483
Review Article

Computational Perspectives into Plasmepsins Structure—Function Relationship: Implications to Inhibitors Design

1Laboratorio de Biología Computacional y Diseño de Proteínas, Centro de Estudio de Proteínas (CEP), Facultad de Biología, Universidad de La Habana, Cuba
2Instituto de Biofísica Carlos Chagas Filho, Universidad Federal do Rio de Janeiro, Brazil

Received 1 February 2011; Revised 1 May 2011; Accepted 3 May 2011

Academic Editor: Gerd Pluschke

Copyright © 2011 Alejandro Gil L. et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. S. H. Kappe, A. M. Vaughan, J. A. Boddey, and A. F. Cowman, “That was then but this is now: malaria research in the time of an eradication agenda,” Science, vol. 328, no. 5980, pp. 862–866, 2010. View at Publisher · View at Google Scholar · View at Scopus
  2. G. H. Coombs, D. E. Goldberg, M. Klemba, C. Berry, J. Kay, and J. C. Mottram, “Aspartic proteases of Plasmodium falciparum and other parasitic protozoa as drug targets,” Trends in Parasitology, vol. 17, no. 11, pp. 532–537, 2001. View at Publisher · View at Google Scholar · View at Scopus
  3. K. Na-Bangchang and J. Karbwang, “Current status of malaria chemotherapy and the role of pharmacology in antimalarial drug research and development,” Fundamental and Clinical Pharmacology, vol. 23, no. 4, pp. 387–409, 2009. View at Publisher · View at Google Scholar · View at Scopus
  4. T. Luksch, A. Blum, N. Klee, W. E. Diederich, C. A. Sotriffer, and G. Klebe, “Pyrrolidine derivatives as plasmepsin inhibitors: binding mode analysis assisted by molecular dynamics simulations of a highly flexible protein,” ChemMedChem, vol. 5, no. 3, pp. 443–454, 2010. View at Publisher · View at Google Scholar · View at Scopus
  5. P. A. Valiente, P. R. Batista, A. Pupo, T. Pons, A. Valencia, and P. G. Pascutti, “Predicting functional residues in Plasmodium falciparum plasmepsins by combining sequence and structural analysis with molecular dynamics simulations,” Proteins, vol. 73, no. 2, pp. 440–457, 2008. View at Publisher · View at Google Scholar · View at Scopus
  6. R. Bhargavi, G. M. Sastry, U. S. Murty, and G. N. Sastry, “Structural and active site analysis of plasmepsins of Plasmodium falciparum: potential anti-malarial targets,” International Journal of Biological Macromolecules, vol. 37, no. 1-2, pp. 73–84, 2005. View at Publisher · View at Google Scholar · View at Scopus
  7. D. E. Goldberg, A. F. Slater, A. Cerami, and G. B. Henderson, “Hemoglobin degradation in the malaria parasite Plasmodium falciparum: an ordered process in a unique organelle,” Proceedings of the National Academy of Sciences of the United States of America, vol. 87, no. 8, pp. 2931–2935, 1990. View at Google Scholar · View at Scopus
  8. D. E. Goldberg, A. F. Slater, R. Beavis, B. Chait, A. Cerami, and G. B. Henderson, “Hemoglobin degradation in the human malaria pathogen Plasmodium falciparum: a catabolic pathway initiated by a specific aspartic protease,” Journal of Experimental Medicine, vol. 173, no. 4, pp. 961–969, 1991. View at Google Scholar · View at Scopus
  9. I. Y. Gluzman, S. E. Francis, A. Oksman, C. E. Smith, K. L. Duffin, and D. E. Goldberg, “Order and specificity of the Plasmodium falciparum hemoglobin degradation pathway,” Journal of Clinical Investigation, vol. 93, no. 4, pp. 1602–1608, 1994. View at Google Scholar · View at Scopus
  10. J. B. Dame, G. R. Reddy, C. A. Yowell, B. M. Dunn, J. Kay, and C. Berry, “Sequence, expression and modeled structure of an aspartic proteinase from the human malaria parasite Plasmodium falciparum,” Molecular and Biochemical Parasitology, vol. 64, no. 2, pp. 177–190, 1994. View at Publisher · View at Google Scholar · View at Scopus
  11. M. J. Humphreys, R. P. Moon, A. Klinder et al., “The aspartic proteinase from the rodent parasite Plasmodium berghei as a potential model for plasmepsins from the human malaria parasite, Plasmodium falciparum,” FEBS Letters, vol. 463, no. 1-2, pp. 43–48, 1999. View at Publisher · View at Google Scholar
  12. F. Salas, J. Fichmann, G. K. Lee, M. D. Scott, and P. J. Rosenthal, “Functional expression of falcipain, a Plasmodium falciparum cysteine proteinase, supports its role as a malarial hemoglobinase,” Infection and Immunity, vol. 63, no. 6, pp. 2120–2125, 1995. View at Google Scholar
  13. P. S. Sijwali, K. Kato, K. B. Seydel et al., “Plasmodium falciparum cysteine protease falcipain-1 is not essential in erythrocytic stage malaria parasites,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 23, pp. 8721–8726, 2004. View at Publisher · View at Google Scholar · View at Scopus
  14. B. R. Shenai, P. S. Sijwali, A. Singh, and P. J. Rosenthal, “Characterization of native and recombinant falcipain-2, a principal trophozoite cysteine protease and essential hemoglobinase of Plasmodium falciparum,” Journal of Biological Chemistry, vol. 275, no. 37, pp. 29000–29010, 2000. View at Google Scholar
  15. P. S. Sijwali, B. R. Shenai, J. Gut, A. Singh, and P. J. Rosenthal, “Expression and characterization of the Plasmodium falciparum haemoglobinase falcipain-3,” Biochemical Journal, vol. 360, no. 2, pp. 481–489, 2001. View at Publisher · View at Google Scholar · View at Scopus
  16. K. K. Eggleson, K. L. Duffin, and D. E. Goldberg, “Identification and characterization of falcilysin, a metallopeptidase involved in hemoglobin catabolism within the malaria parasite Plasmodium falciparum,” Journal of Biological Chemistry, vol. 274, no. 45, pp. 32411–32417, 1999. View at Publisher · View at Google Scholar · View at Scopus
  17. M. Klemba, I. Gluzman, and D. E. Goldberg, “A Plasmodium falciparum dipeptidyl aminopeptidase I participates in vacuolar hemoglobin degradation,” Journal of The Biological Chemistry, vol. 279, no. 41, pp. 43000–43007, 2004. View at Publisher · View at Google Scholar · View at Scopus
  18. A. M. Silva, A. Y. Lee, S. V. Gulnik et al., “Structure and inhibition of plasmepsin II, a hemoglobin-degrading enzyme from Plasmodium falciparum,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 19, pp. 10034–10039, 1996. View at Publisher · View at Google Scholar · View at Scopus
  19. O. A. Asojo, S. V. Gulnik, E. Afonina et al., “Novel uncomplexed and complexed structures of plasmepsin II, an aspartic protease from Plasmodium falciparum,” Journal of Molecular Biology, vol. 327, no. 1, pp. 173–181, 2003. View at Publisher · View at Google Scholar · View at Scopus
  20. O. A. Asojo, E. Afonina, S. V. Gulnik et al., “Structures of ser205 mutant plasmepsin II from Plasmodium falciparum at 1.8 Å in complex with the inhibitors rs367 and rs370,” Acta Crystallographica Section D, vol. 58, no. 12, pp. 2001–2008, 2002. View at Publisher · View at Google Scholar
  21. C. Boss, S. Richard-Bildstein, T. Weller et al., “Inhibitors of the Plasmodium falciparum parasite aspartic protease plasmepsin II: as potential antimalarial agents,” Current Medicinal Chemistry, vol. 10, pp. 883–883, 2003. View at Google Scholar
  22. K. Ersmark, I. Feierberg, S. Bjelic et al., “C-symmetric inhibitors of Plasmodium falciparum plasmepsin II: synthesis and theoretical predictions,” Bioorganic and Medicinal Chemistry, vol. 11, no. 17, pp. 3723–3733, 2003. View at Publisher · View at Google Scholar · View at Scopus
  23. K. Ersmark, I. Feierberg, S. Bjelic et al., “Potent inhibitors of the Plasmodium falciparum enzymes plasmepsin I and II devoid of cathepsin D inhibitory activity,” Journal of Medicinal Chemistry, vol. 47, no. 1, pp. 110–122, 2004. View at Publisher · View at Google Scholar
  24. A. Kiso, K. Hidaka, T. Kimura et al., “Search for substrate-based inhibitors fitting the S2' space of malarial aspartic protease plasmepsin II,” Journal of Peptide Science, vol. 10, no. 11, pp. 641–647, 2004. View at Publisher · View at Google Scholar · View at Scopus
  25. K. Ersmark, B. Samuelsson, and A. Hallberg, “Plasmepsins as potential targets for new antimalarial therapy,” Medicinal Research Reviews, vol. 26, no. 5, pp. 626–666, 2006. View at Publisher · View at Google Scholar
  26. G. H. Coombs, D. E. Goldberg, M. Klemba, C. Berry, J. Kay, and J. C. Mottram, “Aspartic proteases of Plasmodium falciparum and other parasitic protozoa as drug targets,” Trends in Parasitology, vol. 17, no. 11, pp. 532–537, 2001. View at Publisher · View at Google Scholar
  27. V. Zoete, A. Grosdidier, and O. Michielin, “Docking, virtual high throughput screening and in silico fragment-based drug design,” Journal of Cellular and Molecular Medicine, vol. 13, no. 2, pp. 238–248, 2009. View at Publisher · View at Google Scholar · View at Scopus
  28. F. Gagliardi, B. Jones, F. Grey, M. E. Begin, and M. Heikkurinen, “Building an infrastructure for scientific grid computing: status and goals of the EGEE project,” Philosophical Transactions of the Royal Society A, vol. 363, no. 1833, pp. 1729–1742, 2005. View at Publisher · View at Google Scholar · View at Scopus
  29. V. Kasam, M. Zimmermann, A. Maaß et al., “Design of new plasmepsin inhibitors: a virtual high throughput screening approach on the EGEE grid,” Journal of Chemical Information and Modeling, vol. 47, no. 5, pp. 1818–1828, 2007. View at Publisher · View at Google Scholar · View at Scopus
  30. J. Åqvist, C. Medina, and J.-E. Samuelsson, “A new method for predicting binding affinity in computer-aided drug design,” Protein Engineering, vol. 7, no. 3, pp. 385–391, 1994. View at Google Scholar · View at Scopus
  31. S. E. Francis, L. Y. Gluzman, A. Oksman et al., “Molecular characterization and inhibition of a Plasmodium falciparum aspartic hemoglobinase,” The EMBO Journal, vol. 13, no. 2, pp. 306–317, 1994. View at Google Scholar · View at Scopus
  32. R. P. Moon, L. Tyas, U. Certa et al., “Expression and characterisation of plasmepsin I from Plasmodium falciparum,” European Journal of Biochemistry, vol. 244, no. 2, pp. 552–560, 1997. View at Google Scholar · View at Scopus
  33. S. Soni, S. Dhawan, K. M. Rosen, M. Chafel, A. H. Chishti, and M. Hanspal, “Characterization of events preceding the release of malaria parasite from the host red blood cell,” Blood Cells, Molecules, and Diseases, vol. 35, no. 2, pp. 201–211, 2005. View at Publisher · View at Google Scholar · View at Scopus
  34. R. Banerjee and D. E. Goldberg, “The Plasmodium food vacuole,” in Antimalarial Chemotherapy: Mechanisms of Action, Resistance, and New Directions in Drug Discovery, P. J. Rosenthal, Ed., pp. 43–63, Humana Press, Totowa, NJ, USA, 2001. View at Google Scholar
  35. P. J. Rosenthal, “Protease inhibitors,” in Antimalarial Chemotherapy: Mechanisms of Action, Resistance, and New Directions in Drug Discovery, P. J. Rosenthal, Ed., pp. 325–345, Humana Press, Totowa, NJ, USA, 2001. View at Google Scholar
  36. T. S. Haque, A. G. Skillman, C. E. Lee et al., “Potent, low-molecular-weight non-peptide inhibitors of malarial aspartyl protease plasmepsin II,” Journal of Medicinal Chemistry, vol. 42, no. 8, pp. 1428–1440, 1999. View at Publisher · View at Google Scholar
  37. M. J. Gardner, N. Hall, E. Fung et al., “Genome sequence of the human malaria parasite Plasmodium falciparum,” Nature, vol. 419, no. 6906, pp. 498–511, 2002. View at Publisher · View at Google Scholar · View at Scopus
  38. R. Banerjee, J. Liu, W. Beatty, L. Pelosof, M. Klemba, and D. E. Goldberg, “Four plasmepsins are active in the Plasmodium falciparum food vacuole, including a protease with an active-site histidine,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 2, pp. 990–995, 2002. View at Publisher · View at Google Scholar · View at Scopus
  39. K. E. Luker, S. E. Francis, I. Y. Gluzman, and D. E. Goldberg, “Kinetic analysis of plasmepsins I and II, aspartic proteases of the Plasmodium falciparum digestive vacuole,” Molecular and Biochemical Parasitology, vol. 79, no. 1, pp. 71–78, 1996. View at Publisher · View at Google Scholar
  40. D. M. Wyatt and C. Berry, “Activity and inhibition of plasmepsin IV, a new aspartic proteinase from the malaria parasite, Plasmodium falciparum,” FEBS Letters, vol. 513, no. 2-3, pp. 159–162, 2002. View at Publisher · View at Google Scholar
  41. I. Russo, S. Babbitt, V. Muralidharan, T. Butler, A. Oksman, and D. E. Goldberg, “Plasmepsin V licenses Plasmodium proteins for export into the host erythrocyte,” Nature, vol. 463, no. 7281, pp. 632–636, 2010. View at Publisher · View at Google Scholar · View at Scopus
  42. J. Westling, C. A. Yowell, P. Majer, J. W. Erickson, J. B. Dame, and B. M. Dunn, “Plasmodium falciparum, P. vivax, and P. malariae: a comparison of the active site properties of plasmepsins cloned and expressed from three different species of the malaria parasite,” Experimental Parasitology, vol. 87, no. 3, pp. 185–193, 1997. View at Publisher · View at Google Scholar
  43. J. B. Dame, C. A. Yowell, J. M. R. Carlton et al., “Comparative studies of five plasmepsins derived from the human malaria parasites P. falciparum, P. vivax, P.malariae and P.ovalae,” in Molecular Parasitology Meeting VIII Abstrac, Woods Hole, Mass, USA, 1997. View at Google Scholar
  44. T. Li, C. A. Yowell, B. B. Beyer et al., “Recombinant expression and enzymatic subsite characterization of plasmepsin 4 from the four Plasmodium species infecting man,” Molecular and Biochemical Parasitology, vol. 135, no. 1, pp. 101–109, 2004. View at Publisher · View at Google Scholar · View at Scopus
  45. A. Nezami, T. Kimura, K. Hidaka et al., “High-affinity inhibition of a family of Plasmodium falciparum proteases by a designed adaptive inhibitor,” Biochemistry, vol. 42, no. 28, pp. 8459–8464, 2003. View at Publisher · View at Google Scholar
  46. B. B. Beyer, J. V. Johnson, A. Y. Chung et al., “Active-site specificity of digestive aspartic peptidases from the four species of Plasmodium that infect humans using chromogenic combinatorial peptide libraries,” Biochemistry, vol. 44, no. 6, pp. 1768–1779, 2005. View at Publisher · View at Google Scholar · View at Scopus
  47. J. B. Dame, C. A. Yowell, L. Omara-Opyene, J. M. Carlton, R. A. Cooper, and T. Li, “Plasmepsin 4, the food vacuole aspartic proteinase found in all Plasmodium spp. infecting man,” Molecular and Biochemical Parasitology, vol. 130, no. 1, pp. 1–12, 2003. View at Publisher · View at Google Scholar
  48. A. Nezami and E. Freire, “The integration of genomic and structural information in the development of high affinity plasmepsin inhibitors,” International Journal for Parasitology, vol. 32, no. 13, pp. 1669–1676, 2002. View at Publisher · View at Google Scholar · View at Scopus
  49. S. E. Francis, L. Y. Gluzman, A. Oksman et al., “Molecular characterization and inhibition of a Plasmodium falciparum aspartic hemoglobinase,” The EMBO Journal, vol. 13, no. 2, pp. 306–317, 1994. View at Google Scholar · View at Scopus
  50. B. M. Dunn, “Structure and mechanism of the pepsin-like family of aspartic peptidases,” Chemical Reviews, vol. 102, no. 12, pp. 4431–4458, 2002. View at Publisher · View at Google Scholar · View at Scopus
  51. P. Bhaumik, H. Xiao, C. L. Parr et al., “Crystal structures of the histo-aspartic protease (HAP) from Plasmodium falciparum,” Journal of Molecular Biology, vol. 388, no. 3, pp. 520–540, 2009. View at Publisher · View at Google Scholar · View at Scopus
  52. J. Liu, E. S. Istvan, and D. E. Goldberg, “Hemoglobin-degrading plasmepsin II is active as a monomer,” Journal of Biological Chemistry, vol. 281, no. 50, pp. 38682–38688, 2006. View at Publisher · View at Google Scholar · View at Scopus
  53. A. Nezami, T. Kimura, K. Hidaka et al., “High-affinity inhibition of a family of Plasmodium falciparum proteases by a designed adaptive inhibitor,” Biochemistry, vol. 42, no. 28, pp. 8459–8464, 2003. View at Publisher · View at Google Scholar · View at Scopus
  54. A. Nezami and E. Freire, “The integration of genomic and structural information in the development of high affinity plasmepsin inhibitors,” International Journal for Parasitology, vol. 32, no. 13, pp. 1669–1676, 2002. View at Publisher · View at Google Scholar · View at Scopus
  55. K. M. Orrling, M. R. Marzahn, H. Gutiérrez-de-Terán, J. Åqvist, B. M. Dunn, and M. Larhed, “α-substituted norstatines as the transition-state mimic in inhibitors of multiple digestive vacuole malaria aspartic proteases,” Bioorganic and Medicinal Chemistry, vol. 17, no. 16, pp. 5933–5949, 2009. View at Publisher · View at Google Scholar · View at Scopus
  56. H. Gutiérrez-de-Terán, M. Nervall, B. M. Dunn, J. C. Clemente, and J. Åqvist, “Computational analysis of plasmepsin IV bound to an allophenylnorstatine inhibitor,” FEBS Letters, vol. 580, no. 25, pp. 5910–5916, 2006. View at Publisher · View at Google Scholar · View at Scopus
  57. H. Gutiérrez-de-Terán, M. Nervall, K. Ersmark et al., “Inhibitor binding to the plasmepsin IV aspartic protease from Plasmodium falciparum,” Biochemistry, vol. 45, no. 35, pp. 10529–10541, 2006. View at Publisher · View at Google Scholar · View at Scopus
  58. K. Ersmark, M. Nervall, H. Gutiérrez-de-Terán et al., “Macrocyclic inhibitors of the malarial aspartic proteases plasmepsin I, II, and IV,” Bioorganic and Medicinal Chemistry, vol. 14, no. 7, pp. 2197–2208, 2006. View at Publisher · View at Google Scholar · View at Scopus
  59. A. L. Omara-Opyene, P. A. Moura, C. R. Sulsona et al., “Genetic disruption of the Plasmodium falciparum digestive vacuole plasmepsins demonstrates their functional redundancy,” Journal of Biological Chemistry, vol. 279, no. 52, pp. 54088–54096, 2004. View at Publisher · View at Google Scholar · View at Scopus
  60. J. Liu, I. Y. Gluzman, M. E. Drew, and D. E. Goldberg, “The role of Plasmodium falciparum food vacuole plasmepsins,” Journal of Biological Chemistry, vol. 280, no. 2, pp. 1432–1437, 2005. View at Publisher · View at Google Scholar · View at Scopus
  61. J. Liu, E. S. Istvan, I. Y. Gluzman, J. Gross, and D. E. Goldberg, “Plasmodium falciparum ensures its amino acid supply with multiple acquisition pathways and redundant proteolytic enzyme systems,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 23, pp. 8840–8845, 2006. View at Publisher · View at Google Scholar · View at Scopus
  62. J. A. Bonilla, T. D. Bonilla, C. A. Yowell, H. Fujioka, and J. B. Dame, “Critical roles for the digestive vacuole plasmepsins of Plasmodium falciparum in vacuolar function,” Molecular Microbiology, vol. 65, no. 1, pp. 64–75, 2007. View at Publisher · View at Google Scholar · View at Scopus
  63. P. A. Moura, J. B. Dame, and D. A. Fidock, “Role of Plasmodium falciparum digestive vacuole plasmepsins in the specificity and antimalarial mode of action of cysteine and aspartic protease inhibitors,” Antimicrobial Agents and Chemotherapy, vol. 53, no. 12, pp. 4968–4978, 2009. View at Publisher · View at Google Scholar · View at Scopus
  64. T. Luksch, N. S. Chan, S. Brass, C. A. Sotriffer, G. Klebe, and W. E. Diederich, “Computer-aided design and synthesis of nonpeptidic plasmepsin II and IV inhibitors,” ChemMedChem, vol. 3, no. 9, pp. 1323–1336, 2008. View at Publisher · View at Google Scholar · View at Scopus
  65. K. Ersmark, I. Feierberg, S. Bjelic et al., “Potent inhibitors of the Plasmodium falciparum enzymes plasmepsin I and II devoid of cathepsin D inhibitory activity,” Journal of Medicinal Chemistry, vol. 47, no. 1, pp. 110–122, 2004. View at Publisher · View at Google Scholar · View at Scopus
  66. K. Ersmark, I. Feierberg, S. Bjelic et al., “C2-symmetric inhibitors of Plasmodium falciparum plasmepsin II: synthesis and theoretical predictions,” Bioorganic and Medicinal Chemistry, vol. 11, no. 17, pp. 3723–3733, 2003. View at Publisher · View at Google Scholar · View at Scopus
  67. S. Weik, T. Luksch, A. Evers et al., “The potential of P1 site alterations in peptidomimetic protease inhibitors as suggested by virtual screening and explored by the use of C-C-coupling reagents,” ChemMedChem, vol. 1, no. 4, pp. 445–457, 2006. View at Publisher · View at Google Scholar · View at Scopus
  68. K. Ersmark, M. Nervall, E. Hamelink et al., “Synthesis of malarial plasmepsin inhibitors and prediction of binding modes by molecular dynamics simulations,” Journal of Medicinal Chemistry, vol. 48, no. 19, pp. 6090–6106, 2005. View at Publisher · View at Google Scholar · View at Scopus
  69. T. Luksch, N. S. Chan, S. Brass, C. A. Sotriffer, G. Klebe, and W. E. Diederich, “Computer-aided design and synthesis of nonpeptidic plasmepsin II and IV inhibitors,” ChemMedChem, vol. 3, no. 9, pp. 1323–1336, 2008. View at Publisher · View at Google Scholar · View at Scopus
  70. M. G. Bursavich and D. H. Rich, “Designing non-peptide peptidomimetics in the 21st century: inhibitors targeting conformational ensembles,” Journal of Medicinal Chemistry, vol. 45, no. 3, pp. 541–558, 2002. View at Publisher · View at Google Scholar · View at Scopus
  71. G. Casari, C. Sander, and A. Valencia, “A method to predict functional residues in proteins,” Nature Structural Biology, vol. 2, no. 2, pp. 171–178, 1995. View at Publisher · View at Google Scholar · View at Scopus
  72. O. Lichtarge, H. R. Bourne, and F. E. Cohen, “An evolutionary trace method defines binding surfaces common to protein families,” Journal of Molecular Biology, vol. 257, no. 2, pp. 342–358, 1996. View at Publisher · View at Google Scholar · View at Scopus
  73. J. Liu, E. S. Istvan, and D. E. Goldberg, “Hemoglobin-degrading plasmepsin II is active as a monomer,” Journal of Biological Chemistry, vol. 281, no. 50, pp. 38682–38688, 2006. View at Publisher · View at Google Scholar · View at Scopus
  74. A. R. Ortiz, P. Gomez-Puertas, A. Leo-Macias et al., “Computational approaches to model ligand selectivity in drug design,” Current Topics in Medicinal Chemistry, vol. 6, no. 1, pp. 41–55, 2006. View at Publisher · View at Google Scholar · View at Scopus
  75. P. Braiuca, G. Cruciani, C. Ebert, L. Gardossi, and P. Linda, “An innovative application of the "flexible" GRID/PCA computational method: study of differences in selectivity between PGAs from escherichia coli and a providentia rettgeri mutant,” Biotechnology Progress, vol. 20, no. 4, pp. 1025–1031, 2004. View at Publisher · View at Google Scholar · View at Scopus
  76. P. J. Goodford, “A computational procedure for determining energetically favorable binding sites on biologically important macromolecules,” Journal of Medicinal Chemistry, vol. 28, no. 7, pp. 849–857, 1985. View at Google Scholar · View at Scopus
  77. A. Kumar and I. Ghosh, “Mapping selectivity and specificity of active site of plasmepsins from Plasmodium falciparum using molecular interaction field approach,” Protein and Peptide Letters, vol. 14, no. 6, pp. 569–574, 2007. View at Google Scholar · View at Scopus
  78. G. M. Morris, D. S. Goodsell, R. S. Halliday et al., “Automated docking using a lamarckian genetic algorithm and an empirical binding free energy function,” Journal of Computational Chemistry, vol. 19, no. 14, pp. 1639–1662, 1998. View at Google Scholar · View at Scopus
  79. G. M. Morris, H. Ruth, W. Lindstrom et al., “Software news and updates autodock4 and autodocktools4: automated docking with selective receptor flexibility,” Journal of Computational Chemistry, vol. 30, no. 16, pp. 2785–2791, 2009. View at Publisher · View at Google Scholar
  80. I. D. Kuntz, J. M. Blaney, S. J. Oatley, R. Langridge, and T. E. Ferrin, “A geometric approach to macromolecule-ligand interactions,” Journal of Molecular Biology, vol. 161, no. 2, pp. 269–288, 1982. View at Google Scholar · View at Scopus
  81. T. J. Ewing, S. Makino, A. G. Skillman, and I. D. Kuntz, “DOCK 4.0: search strategies for automated molecular docking of flexible molecule databases,” Journal of Computer-Aided Molecular Design, vol. 15, no. 5, pp. 411–428, 2001. View at Publisher · View at Google Scholar · View at Scopus
  82. M. Rarey, B. Kramer, T. Lengauer, and G. Klebe, “A fast flexible docking method using an incremental construction algorithm,” Journal of Molecular Biology, vol. 261, no. 3, pp. 470–489, 1996. View at Publisher · View at Google Scholar · View at Scopus
  83. H. Claußen, C. Buning, M. Rarey, and T. Lengauer, “FLEXE: efficient molecular docking considering protein structure variations,” Journal of Molecular Biology, vol. 308, no. 2, pp. 377–395, 2001. View at Publisher · View at Google Scholar · View at Scopus
  84. R. A. Friesner, J. L. Banks, R. B. Murphy et al., “Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy,” Journal of Medicinal Chemistry, vol. 47, no. 7, pp. 1739–1749, 2004. View at Publisher · View at Google Scholar · View at Scopus
  85. T. A. Halgren, R. B. Murphy, R. A. Friesner et al., “Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening,” Journal of Medicinal Chemistry, vol. 47, no. 7, pp. 1750–1759, 2004. View at Publisher · View at Google Scholar · View at Scopus
  86. G. Jones, P. Willett, R. C. Glen, A. R. Leach, and R. Taylor, “Development and validation of a genetic algorithm for flexible docking,” Journal of Molecular Biology, vol. 267, no. 3, pp. 727–748, 1997. View at Publisher · View at Google Scholar · View at Scopus
  87. M. L. Verdonk, J. C. Cole, M. J. Hartshorn, C. W. Murray, and R. D. Taylor, “Improved protein-ligand docking using GOLD,” Proteins, vol. 52, no. 4, pp. 609–623, 2003. View at Publisher · View at Google Scholar · View at Scopus
  88. C. M. Venkatachalam, X. Jiang, T. Oldfield, and M. Waldman, “LigandFit: a novel method for the shape-directed rapid docking of ligands to protein active sites,” Journal of Molecular Graphics and Modelling, vol. 21, no. 4, pp. 289–307, 2003. View at Publisher · View at Google Scholar · View at Scopus
  89. N. Moitessier, P. Englebienne, D. Lee, J. Lawandi, and C. R. Corbeil, “Towards the development of universal, fast and highly accurate docking/scoring methods: a long way to go,” British Journal of Pharmacology, vol. 153, supplement 1, pp. S7–S26, 2008. View at Publisher · View at Google Scholar · View at Scopus
  90. D. Plewczynski, M. Lazniewski, R. Augustyniak et al., “Can we trust docking results? evaluation of seven commonly used programs on PDBbind database,” Journal of Computational Chemistry, vol. 32, pp. 742–755, 2011. View at Google Scholar
  91. A. N. Jain, “Surflex: fully automatic flexible molecular docking using a molecular similarity-based search engine,” Journal of Medicinal Chemistry, vol. 46, no. 4, pp. 499–511, 2003. View at Publisher · View at Google Scholar · View at Scopus
  92. Z. Zsoldos, D. Reid, A. Simon, S. B. Sadjad, and A. P. Johnson, “eHiTS: a new fast, exhaustive flexible ligand docking system,” Journal of Molecular Graphics and Modelling, vol. 26, no. 1, pp. 198–212, 2007. View at Publisher · View at Google Scholar · View at Scopus
  93. S. Jiang, S. T. Prigge, L. Wei et al., “New class of small nonpeptidyl compounds blocks Plasmodium falciparum development in vitro by inhibiting plasmepsins,” Antimicrobial Agents and Chemotherapy, vol. 45, no. 9, pp. 2577–2584, 2001. View at Publisher · View at Google Scholar · View at Scopus
  94. B. B. Beyer, J. V. Johnson, A. Y. Chung et al., “Active-site specificity of digestive aspartic peptidases from the four species of Plasmodium that infect humans using chromogenic combinatorial peptide libraries,” Biochemistry, vol. 44, no. 6, pp. 1768–1779, 2005. View at Publisher · View at Google Scholar · View at Scopus
  95. S. Bjelic and J. Åqvist, “Computational prediction of structure, substrate binding mode, mechanism, and rate for a malaria protease with a novel type of active site,” Biochemistry, vol. 43, no. 46, pp. 14521–14528, 2004. View at Publisher · View at Google Scholar · View at Scopus
  96. M. M. Kesavulu, A. S. Prakasha-Gowda, T. N. C. Ramya, N. Surolia, and K. Suguna, “Plasmepsin inhibitors: design, synthesis, inhibitory studies and crystal structure analysis,” Journal of Peptide Research, vol. 66, no. 4, pp. 211–219, 2005. View at Publisher · View at Google Scholar · View at Scopus
  97. S. Bjelic and J. Åqvist, “Computational prediction of structure, substrate binding mode, mechanism, and rate for a malaria protease with a novel type of active site,” Biochemistry, vol. 43, no. 46, pp. 14521–14528, 2004. View at Publisher · View at Google Scholar · View at Scopus
  98. P. Liu, M. R. Marzahn, A. H. Robbins et al., “Recombinant plasmepsin 1 from the human malaria parasite Plasmodium falciparum: enzymatic characterization, active site inhibitor design, and structural analysis,” Biochemistry, vol. 48, no. 19, pp. 4086–4099, 2009. View at Publisher · View at Google Scholar · View at Scopus
  99. K. Hidaka, T. Kimura, Y. Tsuchiya et al., “Additional interaction of allophenylnorstatine-containing tripeptidomimetics with malarial aspartic protease plasmepsin II,” Bioorganic and Medicinal Chemistry Letters, vol. 17, no. 11, pp. 3048–3052, 2007. View at Publisher · View at Google Scholar · View at Scopus
  100. S. Y. Huang and X. Zou, “An iterative knowledge-based scoring function to predict protein-ligand interactions: II. Validation of the scoring function,” Journal of Computational Chemistry, vol. 27, no. 15, pp. 1876–1882, 2006. View at Publisher · View at Google Scholar · View at Scopus
  101. I. Muegge and Y. C. Martin, “A general and fast scoring function for protein-ligand interactions: a simplified potential approach,” Journal of Medicinal Chemistry, vol. 42, no. 5, pp. 791–804, 1999. View at Publisher · View at Google Scholar · View at Scopus
  102. H. Gohlke, M. Hendlich, and G. Klebe, “Knowledge-based scoring function to predict protein-ligand interactions,” Journal of Molecular Biology, vol. 295, no. 2, pp. 337–356, 2000. View at Publisher · View at Google Scholar · View at Scopus
  103. H. J. Böhm, “LUDI: rule-based automatic design of new substituents for enzyme inhibitor leads,” Journal of Computer-Aided Molecular Design, vol. 6, no. 6, pp. 593–606, 1992. View at Publisher · View at Google Scholar · View at Scopus
  104. H.-J. Böhm, “The computer program LUDI: a new method for the de novo design of enzyme inhibitors,” Journal of Computer-Aided Molecular Design, vol. 6, no. 1, pp. 61–78, 1992. View at Publisher · View at Google Scholar · View at Scopus
  105. M. D. Eldridge, C. W. Murray, T. R. Auton, G. V. Paolini, and R. P. Mee, “Empirical scoring functions: I. The development of a fast empirical scoring function to estimate the binding affinity of ligands in receptor complexes,” Journal of Computer-Aided Molecular Design, vol. 11, no. 5, pp. 425–445, 1997. View at Google Scholar · View at Scopus
  106. R. Wang, L. Lai, and S. Wang, “Further development and validation of empirical scoring functions for structure-based binding affinity prediction,” Journal of Computer-Aided Molecular Design, vol. 16, no. 1, pp. 11–26, 2002. View at Publisher · View at Google Scholar · View at Scopus
  107. D. Huang and A. Caflisch, “Efficient evaluation of binding free energy using continuum electrostatics solvation,” Journal of Medicinal Chemistry, vol. 47, no. 23, pp. 5791–5797, 2004. View at Publisher · View at Google Scholar · View at Scopus
  108. B. K. Shoichet, A. R. Leach, and I. D. Kuntz, “Ligand solvation in molecular docking,” Proteins, vol. 34, no. 1, pp. 4–16, 1999. View at Publisher · View at Google Scholar · View at Scopus
  109. S.-Y. Huang, S. Z. Grinter, and X. Zou, “Scoring functions and their evaluation methods for protein-ligand docking: recent advances and future directions,” Physical Chemistry Chemical Physics, vol. 12, no. 40, pp. 12899–12908, 2010. View at Publisher · View at Google Scholar
  110. C. W. Murray, T. R. Auton, and M. D. Eldridge, “Empirical scoring functions. II. The testing of an empirical scoring function for the prediction of ligand-receptor binding affinities and the use of bayesian regression to improve the quality of the model,” Journal of Computer-Aided Molecular Design, vol. 12, no. 5, pp. 503–519, 1998. View at Google Scholar
  111. H. Gutiérrez-de-Terán, M. Nervall, K. Ersmark et al., “Inhibitor binding to the plasmepsin IV aspartic protease from Plasmodium falciparum,” Biochemistry, vol. 45, no. 35, pp. 10529–10541, 2006. View at Publisher · View at Google Scholar · View at Scopus
  112. K. T. Andrews, D. P. Fairlie, P. K. Madala et al., “Potencies of human immunodeficiency virus protease inhibitors in vitro against Plasmodium falciparum and in vivo against murine malaria,” Antimicrobial Agents and Chemotherapy, vol. 50, no. 2, pp. 639–648, 2006. View at Publisher · View at Google Scholar · View at Scopus
  113. J. Marelius, K. B. Ljungberg, and J. Åqvist, “Sensitivity of an empirical affinity scoring function to changes in receptor-ligand complex conformations,” European Journal of Pharmaceutical Sciences, vol. 14, no. 1, pp. 87–95, 2001. View at Publisher · View at Google Scholar
  114. A. Wolf, M. Zimmermann, and M. Hofmann-Apitius, “Alternative to consensus scoring—a new approach toward the qualitative combination of docking algorithms,” Journal of Chemical Information and Modeling, vol. 47, no. 3, pp. 1036–1044, 2007. View at Publisher · View at Google Scholar · View at Scopus
  115. D. B. Kitchen, H. Decornez, J. R. Furr, and J. Bajorath, “Docking and scoring in virtual screening for drug discovery: methods and applications,” Nature Reviews Drug Discovery, vol. 3, no. 11, pp. 935–949, 2004. View at Publisher · View at Google Scholar · View at Scopus
  116. G. J. Crowther, A. J. Napuli, J. H. Gilligan et al., “Identification of inhibitors for putative malaria drug targets among novel antimalarial compounds,” Molecular and Biochemical Parasitology, vol. 175, no. 1, pp. 21–29, 2011. View at Publisher · View at Google Scholar
  117. C. D. Carroll and M. Orlowski, “Screening aspartyl proteases with combinatorial libraries,” Advances in Experimental Medicine and Biology, vol. 436, pp. 375–380, 1998. View at Google Scholar · View at Scopus
  118. C. McInnes, “Virtual screening strategies in drug discovery,” Current Opinion in Chemical Biology, vol. 11, no. 5, pp. 494–502, 2007. View at Publisher · View at Google Scholar · View at Scopus
  119. G. Schneider, “Trends in virtual combinatorial library design,” Current Medicinal Chemistry, vol. 9, no. 23, pp. 2095–2101, 2002. View at Google Scholar · View at Scopus
  120. G. Klebe, “Virtual ligand screening: strategies, perspectives and limitations,” Drug Discovery Today, vol. 11, no. 13-14, pp. 580–594, 2006. View at Publisher · View at Google Scholar · View at Scopus
  121. V. Kasam, J. Salzemann, M. Botha et al., “WISDOM-II: screening against multiple targets implicated in malaria using computational grid infrastructures,” Malaria Journal, vol. 8, no. 1, article 88, 2009. View at Publisher · View at Google Scholar · View at Scopus
  122. D. Huanga and A. Caflischa, “Library screening by fragment-based docking,” Journal of Molecular Recognition, vol. 23, no. 2, pp. 183–193, 2010. View at Publisher · View at Google Scholar · View at Scopus
  123. G. Schneider and U. Fechner, “Computer-based de novo design of drug-like molecules,” Nature Reviews Drug Discovery, vol. 4, no. 8, pp. 649–663, 2005. View at Publisher · View at Google Scholar · View at Scopus
  124. P. K. Weiner and P. A. Kollman, “AMBER: assisted model building with energy refinement. A general program for modeling molecules and their interactions,” Journal of Computational Chemistry, vol. 2, pp. 287–303, 1981. View at Google Scholar
  125. R. Friedman and A. Caflisch, “Discovery of plasmepsin inhibitors by fragment-based docking and consensus scoring,” ChemMedChem, vol. 4, no. 8, pp. 1317–1326, 2009. View at Publisher · View at Google Scholar · View at Scopus
  126. B. O. Brandsdal, F. Österberg, M. Almlöf, I. Feierberg, V. B. Luzhkov, and J. Åqvist, “Free energy calculations and ligand binding,” Advances in Protein Chemistry, vol. 66, pp. 123–158, 2003. View at Publisher · View at Google Scholar · View at Scopus
  127. P. A. Kollman, “Free energy calculations: applications to chemical and biochemical phenomena,” Chemical Reviews, vol. 93, no. 7, pp. 2395–2417, 1993. View at Google Scholar · View at Scopus
  128. D. L. Beveridge and F. M. Dicapua, “Free energy via molecular simulation: applications to chemical and biomolecular systems,” Annual Review of Biophysics and Biophysical Chemistry, vol. 18, pp. 431–492, 1989. View at Google Scholar · View at Scopus
  129. J. Åqvist, V. B. Luzhkov, and B. O. Brandsdal, “Ligand binding affinities from MD simulations,” Accounts of Chemical Research, vol. 35, no. 6, pp. 358–365, 2002. View at Publisher · View at Google Scholar · View at Scopus
  130. J. Åqvist and J. Marelius, “The linear interaction energy method for predicting ligand binding free energies,” Combinatorial Chemistry and High Throughput Screening, vol. 4, no. 8, pp. 613–626, 2001. View at Google Scholar · View at Scopus
  131. Y. Tominaga and W. L. Jorgensen, “General model for estimation of the inhibition of protein kinases using monte carlo simulations,” Journal of Medicinal Chemistry, vol. 47, no. 10, pp. 2534–2549, 2004. View at Publisher · View at Google Scholar · View at Scopus
  132. R. Zhou, R. Friesner, A. Ghosh, R. C. Rizzo, W. L. Jorgensen, and R. M. Levy, “New linear interaction method for binding affinity calculations using a continuum solvent model,” Journal of Physical Chemistry B, vol. 105, no. 42, pp. 10388–10397, 2001. View at Publisher · View at Google Scholar · View at Scopus
  133. V. Zoete, O. Michielin, and M. Karplus, “Protein-ligand binding free energy estimation using molecular mechanics and continuum electrostatics. Application to HIV-1 protease inhibitors,” Journal of Computer-Aided Molecular Design, vol. 17, no. 12, pp. 861–880, 2003. View at Google Scholar
  134. T. Hansson, J. Marelius, and J. Åqvist, “Ligand binding affinity prediction by linear interaction energy methods,” Journal of Computer-Aided Molecular Design, vol. 12, no. 1, pp. 27–35, 1998. View at Google Scholar · View at Scopus
  135. J. Marelius, T. Hansson, and J. Åqvist, “Calculation of ligand binding free energies from molecular dynamics simulations,” International Journal of Quantum Chemistry, vol. 69, no. 1, pp. 77–88, 1998. View at Google Scholar · View at Scopus
  136. P. J. Loida, in Chemistry, p. 123, Universiy of Illionis, Urbana, Ill, USA, 1994.
  137. W. Wang, J. Wang, and P. A. Kollman, “What determines the van der waals coefficient β in the LIE (linear interaction energy) method to estimate binding free energies using molecular dynamics simulations?” Proteins, vol. 34, no. 3, pp. 395–402, 1999. View at Publisher · View at Google Scholar · View at Scopus
  138. M. D. Paulsen and R. L. Ornstein, “Binding free energy calculations for P450cam-substrate complexes,” Protein Engineering, vol. 9, no. 7, pp. 567–571, 1996. View at Google Scholar · View at Scopus
  139. M. Almlöf, J. Carlsson, and J. Åqvist, “Improving the accuracy of the linear interaction energy method for solvation free energies,” Journal of Chemical Theory and Computation, vol. 3, no. 6, pp. 2162–2175, 2007. View at Publisher · View at Google Scholar
  140. P. A. Valiente, A. Gil, P. R. Batista, E. R. Caffarena, T. Pons, and P. G. Pascutti, “New parameterization approaches of the LIE method to improve free energy calculations of plmll-inhibitors complexes,” Journal of Computational Chemistry, vol. 31, no. 15, pp. 2723–2734, 2010. View at Publisher · View at Google Scholar
  141. W. F. van Gunsteren and H. J. C. Berendsen, Groningen Molecular Simulation (GROMOS) Library Manual, Biomos. Nijenborgh 4, University of Groningen, Groningen, The Netherland, 1987.
  142. T. Hansson and J. Åqvist, “Estimation of binding free energies for HIV proteinase inhibitors by molecular dynamics simulations,” Protein Engineering, vol. 8, no. 11, pp. 1137–1144, 1995. View at Google Scholar
  143. J. Hultén, N. M. Bonham, U. Nillroth et al., “Cyclic HIV-1 protease inhibitors derived from mannitol: synthesis, inhibitory potencies, and computational predictions of binding affinities,” Journal of Medicinal Chemistry, vol. 40, no. 6, pp. 885–897, 1997. View at Publisher · View at Google Scholar · View at Scopus
  144. J. Åqvist and S. L. Mowbray, “Sugar recognition by a glucose/galactose receptor. Evaluation of binding energetics from molecular dynamics simulations,” Journal of Biological Chemistry, vol. 270, no. 17, pp. 9978–9981, 1995. View at Google Scholar · View at Scopus
  145. J. Åqvist, “Calculation of absolute binding free energies for charged ligands and effects of long-range electrostatic interactions,” Journal of Computational Chemistry, vol. 17, no. 14, pp. 1587–1597, 1996. View at Google Scholar · View at Scopus
  146. J. Åqvist and T. Hansson, “On the validity of electrostatic linear response in polar solvents,” Journal of Physical Chemistry, vol. 100, no. 22, pp. 9512–9521, 1996. View at Google Scholar · View at Scopus
  147. M. Almlöf, B. O. Brandsdal, and J. Åqvist, “Binding affinity prediction with different force fields: examination of the linear interaction energy method,” Journal of Computational Chemistry, vol. 25, no. 10, pp. 1242–1254, 2004. View at Publisher · View at Google Scholar
  148. J. Marelius, M. Graffner-Nordberg, T. Hansson et al., “Computation of affinity and selectivity: binding of 2,4-diaminopteridine and 2,4-diaminoquinazoline inhibitors to dihydrofolate reductases,” Journal of Computer-Aided Molecular Design, vol. 12, no. 2, pp. 119–131, 1998. View at Google Scholar
  149. K. B. Ljungberg, J. Marelius, D. Musil, P. Svensson, B. Norden, and J. Åqvist, “Computational modelling of inhibitor binding to human thrombin,” European Journal of Pharmaceutical Sciences, vol. 12, no. 4, pp. 441–446, 2001. View at Publisher · View at Google Scholar · View at Scopus
  150. H. Gutiérrez-de-Terán, M. Nervall, B. M. Dunn, J. C. Clemente, and J. Åqvist, “Computational analysis of plasmepsin IV bound to an allophenylnorstatine inhibitor,” FEBS Letters, vol. 580, no. 25, pp. 5910–5916, 2006. View at Publisher · View at Google Scholar
  151. L. Prade, A. F. Jones, C. Boss et al., “X-ray structure of plasmepsin II complexed with a potent achiral inhibitor,” Journal of Biological Chemistry, vol. 280, no. 25, pp. 23837–23843, 2005. View at Publisher · View at Google Scholar · View at Scopus
  152. O. A. Asojo, S. V. Gulnik, E. Afonina et al., “Novel uncomplexed and complexed structures of plasmepsin II, an aspartic protease from Plasmodium falciparum,” Journal of Molecular Biology, vol. 327, no. 1, pp. 173–181, 2003. View at Publisher · View at Google Scholar · View at Scopus
  153. O. A. Asojo, E. Afonina, S. V. Gulnik et al., “Structures of ser205 mutant plasmepsin II from Plasmodium falciparum at 1.8 Å in complex with the inhibitors rs367 and rs370,” Acta Crystallographica Section D, vol. 58, no. 12, pp. 2001–2008, 2002. View at Publisher · View at Google Scholar · View at Scopus