YASARA: A Tool to Obtain Structural Guidance in Biocatalytic Investigations

  • Henrik Land
  • Maria Svedendahl HumbleEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1685)


In biocatalysis, structural knowledge regarding an enzyme and its substrate interactions complements and guides experimental investigations. Structural knowledge regarding an enzyme or a biocatalytic reaction system can be generated through computational techniques, such as homology- or molecular modeling. For this type of computational work, a computer program developed for molecular modeling of proteins is required. Here, we describe the use of the program YASARA Structure. Protocols for two specific biocatalytic applications, including both homology modeling and molecular modeling such as energy minimization, molecular docking simulations and molecular dynamics simulations, are shown. The applications are chosen to give realistic examples showing how structural knowledge through homology and molecular modeling is used to guide biocatalytic investigations and protein engineering studies.

Key words

Biocatalysis Enzyme Energy minimization Homology modeling Molecular modeling Molecular docking simulations Molecular dynamics simulations Protein engineering 



This work was funded by KTH Royal Institute of Technology.


  1. 1.
    Faber K (2011) Biotransformations in organic chemistry: a textbook, 6th edn. Springer, HeidelbergCrossRefGoogle Scholar
  2. 2.
    Luetz S, Giver L, Lalonde J (2008) Engineered enzymes for chemical production. Biotechnol Bioeng 101:647–653CrossRefPubMedGoogle Scholar
  3. 3.
    Widmann M, Pleiss J, Samland AK (2012) Computational tools for rational protein engineering of aldolases. Comput Struct Biotechnol J 2:e201209016CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Chen R (2001) Enzyme engineering: rational redesign versus directed evolution. Trends Biotechnol 19:13–15CrossRefPubMedGoogle Scholar
  5. 5.
    Chica RA, Doucet N, Pelletier JN (2005) Semi-rational approaches to engineering enzyme activity: combining the benefits of directed evolution and rational redesign. Curr Opin Biotechnol 16:378–384CrossRefPubMedGoogle Scholar
  6. 6.
    Turner NJ (2009) Directed evolution drives the next generation of biocatalysts. Nat Chem Biol 5:567–573CrossRefPubMedGoogle Scholar
  7. 7.
    Otten LG, Hollmann F, Arends IWCE (2009) Enzyme engineering for enantioselectivity: from trial-and-error to rational design? Trends Biotechnol 28:46–54CrossRefPubMedGoogle Scholar
  8. 8.
    Lutz S (2010) Beyond directed evolution - semi-rational protein engineering and design. Curr Opin Biotechnol 6:734–743CrossRefGoogle Scholar
  9. 9.
    Bommarius AS, Blum JK, Abrahamson MJ (2011) Status of protein engineering for biocatalysts: how to design an industrially useful biocatalyst. Curr Opin Chem Biol 15:194–200CrossRefPubMedGoogle Scholar
  10. 10.
    Bornscheuer UT, Huisman GW, Kazlauskas RJ et al (2012) Engineering the third wave of biocatalysis. Nature 485:185–194CrossRefPubMedGoogle Scholar
  11. 11.
    Steiner K, Schwab H (2012) Recent advances in rational approaches for enzyme engineering. Comput Struct Biotechnol J 2:e201209010CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
  13. 13.
    Bergman HM, Henrick K, Nakamura H (2003) Announcing the world-wide Protein Data Bank. Nat Struct Biol 10:980CrossRefGoogle Scholar
  14. 14.
    Epstain CJ, Goldberger RF, Anfinsen CB (1963) The genetic control of tertiary protein structure: studies with model systems. Cold Spring Harb Symp Quant Biol 28:439–449CrossRefGoogle Scholar
  15. 15.
    Epstain CJ (1964) Relation of protein evolution to tertiary structure. Nature 203:1350–1352CrossRefGoogle Scholar
  16. 16.
    Chothia C, Lesk AM (1986) The relation between the divergence of sequence and structure in proteins. EMBO J 5:823–836PubMedPubMedCentralGoogle Scholar
  17. 17.
    Sander C, Schneider R (1991) Database of homology-derived protein structures and the structural meaning of sequence alignment. Proteins 9:56–68CrossRefPubMedGoogle Scholar
  18. 18.
    Rost B (1999) Twilight zone of protein sequence alignments. Protein Eng 12:85–94CrossRefPubMedGoogle Scholar
  19. 19.
    Krieger E, Nabuurs SB, Vriend G (2003) Homology modeling. In: Bourne PE, Weissig H (eds) Structural bioinformatics. John Wiley & Sons, Hoboken, NJGoogle Scholar
  20. 20.
    Tramontano A (2006) Protein structure prediction. Concepts and applications. Wiley-VCH, WeinheimGoogle Scholar
  21. 21.
    Venselaar H, Joosten RP, Vroling B et al (2010) Homology modeling and spectroscopy, a never ending love story. Eur Biophys J 39:551–563CrossRefPubMedGoogle Scholar
  22. 22.
    Leach AR (2001) Molecular modelling – principles and applications, 2nd edn. Dorset Press, DorchesterGoogle Scholar
  23. 23.
    Information regarding the YASARA program products
  24. 24.
    Krieger E, Vriend G (2014) YASARA View - molecular graphics for all devices - from smartphones to workstations. Bioinformatics 30:2981–2982CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    The NCBI GenBank:
  26. 26.
    Benson DA, Cavanaugh M, Clark K et al (2013) GeneBank. Nucleic Acids Res 41:D36–D42CrossRefPubMedGoogle Scholar
  27. 27.
    Pre-made script in YASARA for homology modeling simulations
  28. 28.
    Altschul SF, Madden TL, Schäffer AA et al (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Hooft RW, Vriend G, Sander C et al (1996) Errors in protein structures. Nature 381:272CrossRefPubMedGoogle Scholar
  30. 30.
    Jones DT (1999) Protein secondary structure prediction based on position-specific scoring matrices. J Mol Biol 292:195–202CrossRefPubMedGoogle Scholar
  31. 31.
    Konagurthu AS, Whisstock JC, Stuckey PJ et al (2006) MUSTANG: a multiple structural alignment algorithm. Proteins 64:559–574CrossRefPubMedGoogle Scholar
  32. 32.
    Denesyuk AI, Denessiouk KA, Korpela T et al (2002) Functional attributes of the phosphate group binding cup of pyridoxal phosphate-dependent enzymes. J Mol Biol 316:155–172CrossRefPubMedGoogle Scholar
  33. 33.
    Sayer C, Isupov MN, Westlake A et al (2013) Structural studies with Pseudomonas and Chromobacterium [omega]-aminotransferases provide insights into their differing substrate specificity. Acta Crystallogr Sect D 69:564–576CrossRefGoogle Scholar
  34. 34.
    Baugh L, Phan I, Begley DW et al (2015) Increasing the structural coverage of tuberculosis drug targets. Tuberculosis 95:142–148CrossRefPubMedGoogle Scholar
  35. 35.
    Silverman RB (2002) The organic chemistry of enzyme-catalysed reactions, 2nd edn. Academic Press, London, pp 388–390Google Scholar
  36. 36.
    Pre-made script in YASARA written by Elmar Krieger for molecular docking simulations
  37. 37.
    Pre-made script in YASARA written by Elmar Krieger to visualize (play up) a molecular docking simulation
  38. 38.
    Svedendahl M, Branneby C, Lindberg L et al (2010) Reversed enantiopreference of an ω-transaminase by a single-point mutation. ChemCatChem 2:976–980CrossRefGoogle Scholar
  39. 39.
    Svedendahl Humble M, Engelmark Cassimjee K, Abedi V et al (2012) Key amino acid residues for reversed or improved enantiospecificity of an ω-transaminase. ChemCatChem 4:1167–1172CrossRefGoogle Scholar
  40. 40.
    Steffen-Munsberg F, Vickers C, Thontowi A et al (2013) Connecting unexplored protein crystal structures to enzymatic function. ChemCatChem 5:150–153CrossRefGoogle Scholar
  41. 41.
    Steffen-Munsberg F, Vickers C, Thontowi A et al (2013) Revealing the structural basis of promiscuous amine transaminase activity. ChemCatChem 5:154–157CrossRefGoogle Scholar
  42. 42.
    Pre-made script in YASARA written by Elmar Krieger for molecular dynamics simulation
  43. 43.
    Pre-made script in YASARA written by Elmar Krieger to visualize (play up) a molecular dynamics simulation

Copyright information

© Springer Science+Business Media LLC 2018

Authors and Affiliations

  1. 1.School of BiotechnologyIndustrial Biotechnology, KTH Royal Institute of Technology, AlbaNova University CenterStockholmSweden
  2. 2.Department of Chemistry, Molecular BiomimeticsUppsala UniversityUppsalaSweden
  3. 3.Pharem Biotech ABSödertäljeSweden

Personalised recommendations