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Protein Structures and Structure-Based Rational Drug Design

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Applied Bioinformatics

Abstract

Proteins are macromolecules whose monomeric subunits are the naturally occurring 20 amino acids. The amino acids are linked via peptide bonds (generated upon water release) to form a polypeptide (► Chap. 1). Polypeptides can range in length from three to several hundred amino acids. The amino acid sequence of a given protein, also known as the primary structure, is genetically determined. It becomes fixed during translation based on the information encoded in the mRNA.

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References

  • Abdulla MH, Lim KC, Sajid M, McKerrow JH, Caffrey CR (2007) Schistosomiasis mansoni: novel chemotherapy using a cysteine protease inhibitor. PLoS Med 4:e14

    Article  Google Scholar 

  • Barr SC, Warner KL, Kornreic BG, Piscitelli J, Wolfe A, Benet L, McKerrow JH (2005) A cysteine protease inhibitor protects dogs from cardiac damage during infection by Trypanosoma cruzi. Antimicrob Agents Chemother 49:5160–5161

    Article  CAS  Google Scholar 

  • Biasini M, Bienert S, Waterhouse A, Arnold K, Studer G, Schmidt T, Kiefer F, Cassarino TG, Bertoni M, Bordoli L, Schwede T (2014) SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Res 42(W1):W252–W258

    Article  CAS  Google Scholar 

  • Biobel G, Sabatini DD (1971) In: Manson LA (ed) Biomembranes. Plenum, New York, pp 193–195

    Chapter  Google Scholar 

  • Burley SK, Bonanno J (2002) Structuring the universe of proteins. Ann Rev Genomics Hum Genet 3:243–262

    Article  CAS  Google Scholar 

  • Dixon SL, Smondyrev AM, Rao SN (2006) PHASE: a novel approach to pharmacophore modeling and 3D database searching. Chem Biol Drug Des 67:370–372

    Article  CAS  Google Scholar 

  • Engel JC, Doyle PS, Hsieh I, McKerrow JH (1998) Cysteine protease inhibitors cure an experimental Trypanosoma cruzi infection. J Exp Med 188:725–734

    Article  CAS  Google Scholar 

  • Ewing TJA, Kuntz ID (1996) Critical evaluation of search algorithms for automated molecular docking and database screening. J Comp Chem 18:1175–1189

    Article  Google Scholar 

  • Fischer E (1894) Einfluss der Configuration auf die Wirkung der Enzyme. Ber Dtsch Chem Ges 27:3189–3232

    Article  CAS  Google Scholar 

  • Jones G, Willett P, Glen RC, Leach AR, Taylor R (1997) Development and validation of a genetic algorithm for flexible docking. J Mol Biol 267:727–748

    Article  CAS  Google Scholar 

  • Khare S, Nagle AS, Biggart A, Lai YH, Liang F, Davis LC, Barnes SW, Mathison CJ, Myburgh E, Gao MY, Gillespie JR, Liu X, Tan JL, Stinson M, Rivera IC, Ballard J, Yeh V, Groessl T, Federe G, Koh HX, Venable JD, Bursulaya B, Shapiro M, Mishra PK, Spraggon G, Brock A, Mottram JC, Buckner FS, Rao SP, Wen BG, Walker JR, Tuntland T, Molteni V, Glynne RJ, Supek F (2016) Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness. Nature 537(7619):229–233

    Article  CAS  Google Scholar 

  • Kitchen DB, Decornez H, Furr JR, Bajorath J (2004) Docking and scoring in virtual screening for drug discovery: methods and applications. Nat Rev Drug Discov 3(11):935–949

    Article  CAS  Google Scholar 

  • Klebe G (2013) Drug design. Springer, Heidelberg

    Book  Google Scholar 

  • Koch O, Jäger T, Heller K, Khandavalli PC, Pretzel J, Becker K, Flohé L, Selzer PM (2013) Identification of M. tuberculosis thioredoxin reductase inhibitors based on high-throughput docking using constraints. J Med Chem 56(12):4849–4859

    Article  CAS  Google Scholar 

  • Lecaille F, Kaleta J, Brömme D (2002) Human and parasitic papain-like cysteine proteases: their role in physiology and pathology and recent developments in inhibitor design. Chem Rev 102:4459–4488

    Article  CAS  Google Scholar 

  • Li H, O’Donoghue AJ, van der Linden WA, Xie SC, Yoo E, Foe IT, Tilley L, Craik CS, da Fonseca PC, Bogyo M (2016) Structure- and function-based design of Plasmodium-selective proteasome inhibitors. Nature 530(7589):233–236

    Article  CAS  Google Scholar 

  • Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ (2009) Autodock4 and AutoDockTools4: automated docking with selective receptor flexiblity. J Comput Chem 16:2785–2791

    Article  Google Scholar 

  • Petersen TN, Brunak S, von Heijne G, Nielsen H (2011) SignalP 4.0: discriminating signal peptides from transmembrane regions. Nat Methods 8:785–786

    Article  CAS  Google Scholar 

  • Rarey M, Kramer B, Lengauer T, Klebe G (1996) A fast flexible docking method using an incremental construction algorithm. J Mol Biol 261:470–489

    Article  CAS  Google Scholar 

  • Selzer PM (2003) Structure-Based-Rational-Drug-Design: Neue Wege der modernen Wirkstoffentwicklung. In: Lucius R, Hiepe T, Gottstein B (eds) Grundzüge der allgemeinen Parasitologie. Parey, Berlin

    Google Scholar 

  • Selzer PM, Chen X, Chan VJ, Cheng M et al (1997) Leishmania major: molecular modeling of cysteine proteases and prediction of new nonpeptide inhibitors. Exp Parasitol 87:212–221

    Article  CAS  Google Scholar 

  • Selzer PM, Pingel S, Hsieh I, Ugele B et al (1999) Cysteine protease inhibitors as chemotherapy: lessons from a parasite target. Proc Natl Acad Sci U S A 96:11015–11022

    Article  CAS  Google Scholar 

  • Shenai BR, Semenov AV, Rosenthal PJ (2002) Stage-specific antimalarial activity of cysteine protease inhibitors. Biol Chem 383:843–847

    Article  CAS  Google Scholar 

  • Westbrook J, Feng Z, Chen L, Yang H, Berman HM (2003) The protein data bank and structural genomics. Nucleic Acids Res 31:489–491

    Article  CAS  Google Scholar 

  • Wolber G, Dornhofer AA, Langer T (2007) Efficient overlay of small organic molecules using 3D pharmacophores. J Comput Aided Mol Des 20(12):773–788

    Article  Google Scholar 

  • Wolber G, Seidel T, Bendix F, Langer T (2008) Molecule-pharmacophore superpositioning and pattern matching in computational drug design. Drug Discov Today 13(1–2):23–29

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Boehringer Ingelheim, Animal Health, Ingelheim am Rhein, Germany

    Paul M. Selzer

  2. MSD Animal Health, Innovation GmbH, Schwabenheim, Germany

    Richard J. Marhöfer

  3. TU Dortmund University, Faculty of Chemistry and Chemical Biology, Dortmund, Germany

    Oliver Koch

Authors
  1. Paul M. Selzer
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  2. Richard J. Marhöfer
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  3. Oliver Koch
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Selzer, P.M., Marhöfer, R.J., Koch, O. (2018). Protein Structures and Structure-Based Rational Drug Design. In: Applied Bioinformatics. Springer, Cham. https://doi.org/10.1007/978-3-319-68301-0_5

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