Molecular Dynamics Simulations to Study Structure-Function Relationship in Psychrophilic Enzymes

Grand Challenges in Biology and Biotechnology

Volumn 1, Issue , 2016, Pages 675-698

  Papaleo, Elena ^a   Tiberti, Matteo ^b   Invernizzi, Gaetano ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b UNIVERSITY OF MILANO BICOCCA   (Italy)

Author keywords

Conformational Ensemble; Force Field; Free Energy Landscape; Millisecond Timescale; Psychrophilic Enzyme

Indexed keywords

EID: 84980356617     PISSN: 23671017     EISSN: 23671025     Source Type: Book Series    
DOI: 10.1007/978-3-319-13521-2_24     Document Type: Chapter

References (96)

1. Acuner Ozbabacan SE, Gursoy A, Keskin O, Nussinov R (2010) Conformational ensembles, signal transduction and residue hot spots: application to drug discovery. Curr Opin Drug Discov Devel 13:527–537
2. Adekoya OA, Helland R, Willassen N-P, Sylte I (2006) Comparative sequence and structure analysis reveal features of cold adaptation of an enzyme in the thermolysin family. Proteins 62:435–449
3. Amadei A, Linssen AB, Berendsen HJ (1993) Essential dynamics of proteins. Proteins 17:412–425
4. Aurilia V, Rioux-Dube JF, Marabotti A, Pezolet M, D’Auria S (2009) Structure and dynamics of cold-adapted enzymes as investigated by FT-IR spectroscopy and MD. The case on an esterase from Pseudoalteromonas haloplanktis. J Phys Chem B 113:7753–7761
5. Badieyan S, Bevan DR, Zhang C (2012) Study and design of stability in GH5 cellulases. Biotechnol Bioeng 109:31–44
6. Baldwin AJ, Kay LE (2009) NMR spectroscopy brings invisible protein states into focus. Nat Chem Biol 5:808–814
7. Barducci A, Pfaendtner J, Bonomi M (2015) Tackling sampling challenges in biomolecular simulations. Methods Mol Biol 1215:151–171
8. Best RB, Zhu X, Shim J et al (2012) Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of the backbone φ, ψ and side-chain χ(1) and χ(2) dihedral angles. J Chem Theory Comput 8:3257–3273
9. Boehr DD, Nussinov R, Wright PE (2009) The role of dynamic conformational ensembles in biomolecular recognition. Nat Chem Biol 5:789–796
10. Brandsdal BO, Heimstad ES, Sylte I, Smalås AO (1999) Comparative molecular dynamics of mesophilic and psychrophilic protein homologues studied by 1.2 ns simulations. J Biomol Struct Dyn 17:493–506
11. Calimet N, Simonson T (2006) Cys(x)His(y)-Zn2+ interactions: possibilities and limitations of a simple pairwise force field. J Mol Graph Model 24:404–411
12. Camilloni C, Vendruscolo M (2014) Statistical mechanics of the denatured state of a protein using replica-averaged metadynamics. J Am Chem Soc 136:8982–8991
13. Camilloni C, Robustelli P, De Simone A et al (2012) Characterization of the conformational equilibrium between the two major substates of RNase A using NMR chemical shifts. J Am Chem Soc 134:3968–3971
14. Camilloni C, Cavalli A, Vendruscolo M (2013) Replica-averaged metadynamics. J Chem Theory Comput 9:5610–5617
15. Cary SC, McDonald IR, Barrett JE, Cowan DA (2010) On the rocks: the microbiology of Antarctic Dry Valley soils. Nat Rev Microbiol 8:129–138
16. Chiuri R, Maiorano G, Rizzello A et al (2009) Exploring local flexibility/rigidity in psychrophilic and mesophilic carbonic anhydrases. Biophys J 96:1586–1596
17. D’Amico S, Marx J-C, Gerday C, Feller G (2003) Activity-stability relationships in extremophilic enzymes. J Biol Chem 278:7891–7896
18. D’Auria S, Aurilia V, Marabotti A, Gonnelli M, Strambini G (2009) Structure and dynamics of cold-adapted enzymes as investigated by phosphorescence spectroscopy. J Phys Chem B 113:13171–13178
19. Debiec KT, Gronenborn AM, Chong LT (2014) Evaluating the strength of salt bridges: a comparison of current biomolecular force fields. J Phys Chem B. doi:10.1021/jp500958r
20. Dror RO, Dirks RM, Grossman JP et al (2012) Biomolecular simulation: a computational microscope for molecular biology. Annu Rev Biophys 41:429–452
21. Eisenmesser EZ, Millet O, Labeikovsky W et al (2005) Intrinsic dynamics of an enzyme underlies catalysis. Nature 438:117–121
22. Eswar N, Eramian D, Webb B et al (2008) Protein structure modeling with MODELLER. Methods Mol Biol 426:145–159
23. Fan H, Mark AE (2004) Refinement of homology-based protein structures by molecular dynamics simulation techniques. Protein Sci 13:211–220
24. Fedøy A-E, Yang N, Martinez A et al (2007) Structural and functional properties of isocitrate dehydrogenase from the psychrophilic bacterium Desulfotalea psychrophila reveal a cold-active enzyme with an unusual high thermal stability. J Mol Biol 372:130–149
25. Feller G, Gerday C (2003) Psychrophilic enzymes: hot topics in cold adaptation. Nat Rev Microbiol 1:200–208
26. Fields PA (2001) Review: protein function at thermal extremes: balancing stability and flexibility. Comp Biochem Physiol A Mol Integr Physiol 129:417–431
27. Fraccalvieri D, Tiberti M, Pandini A (2012) Functional annotation of the mesophilic-like character of mutants in a cold-adapted enzyme by self-organising map analysis of their molecular dynamics. Mol Biosyst 8:2680–2691
28. Fraser JS, Jackson CJ (2011) Mining electron density for functionally relevant protein polysterism in crystal structures. Cell Mol Life Sci 68:1829–1841
29. Ganjalikhany MR, Ranjbar B, Taghavi AH, Tohidi Moghadam T (2012) Functional motions of Candida antarctica lipase B: a survey through open-close conformations. PLoS One 7:e40327
30. Garcia AE (1992) Large-amplitude nonlinear motions in proteins. Phys Rev Lett 68:2696–2699
31. Gerday C, Aittaleb M, Bentahir M et al (2000) Cold-adapted enzymes: from fundamentals to biotechnology. Trends Biotechnol 18:103–107
32. Gianese G, Bossa F, Pascarella S (2002) Comparative structural analysis of psychrophilic and meso-and thermophilic enzymes. Proteins 47:236–249
33. Gu J, Hilser VJ (2009) Sequence-based analysis of protein energy landscapes reveals nonuniform thermal adaptation within the proteome. Mol Biol Evol 26:2217–2227
34. Halgren TA, Damm W (2001) Polarizable force fields. Curr Opin Struct Biol 11:236–242
35. Heidarsson PO, Sigurdsson ST, Asgeirsson B (2009) Structural features and dynamics of a cold-adapted alkaline phosphatase studied by EPR spectroscopy. FEBS J 276:2725–2735
36. Henzler-Wildman K, Kern D (2007) Dynamic personalities of proteins. Nature 450:964–972
37. Henzler-Wildman KA, Lei M, Thai V et al (2007) A hierarchy of timescales in protein dynamics is linked to enzyme catalysis. Nature 450:913–916
38. Hilser VJ, García-Moreno EB, Oas TG et al (2006) A statistical thermodynamic model of the protein ensemble. Chem Rev 106:1545–1558
39. Invernizzi G, Papaleo E, Grandori R et al (2009) Relevance of metal ions for lipase stability: structural rearrangements induced in the Burkholderia glumae lipase by calcium depletion. J Struct Biol 168:562–570
40. Isaksen GV, Åqvist J, Brandsdal BO (2014) Protein surface softness is the origin of enzyme cold-adaptation of trypsin. PLoS Comput Biol 10:e1003813
41. Jónsdóttir LB, Ellertsson BÖ, Invernizzi G et al (2014) The role of salt bridges on the temperature adaptation of aqualysin I, a thermostable subtilisin-like proteinase. Biochim Biophys Acta. doi:10.1016/j.bbapap.2014.08.011
42. Kosugi T, Hayashi S (2012) Crucial role of protein flexibility in formation of a stable reaction transition state in an α-amylase catalysis. J Am Chem Soc 134:7045–7055
43. Leach AR (2001) Molecular modelling. Principles and applications, 2nd edn. Prentice Hall, Harlow/New York
44. Leiros H-KS, Pey AL, Innselset M et al (2007) Structure of phenylalanine hydroxylase from Colwellia psychrerythraea 34H, a monomeric cold active enzyme with local flexibility around the active site and high overall stability. J Biol Chem 282:21973–21986
45. Li P, Roberts BP, Chakravorty DK, Merz KM (2013) Rational design of particle mesh Ewald compatible Lennard-Jones parameters for +2 metal cations in explicit solvent. J Chem Theory Comput 9:2733–2748
46. Lindorff-Larsen K, Piana S, Dror RO, Shaw DE (2011) How fast-folding proteins fold. Science 334:517–520
47. Lindorff-Larsen K, Maragakis P, Piana S et al (2012) Systematic validation of protein force fields against experimental data. PLoS One 7:e32131
48. Ma B, Nussinov R (2010) Enzyme dynamics point to stepwise conformational selection in catalysis. Curr Opin Chem Biol 14:652–659
49. Martinez R, Schwaneberg U, Roccatano D (2011) Temperature effects on structure and dynamics of the psychrophilic protease subtilisin S41 and its thermostable mutants in solution. Protein Eng Des Sel 24:533–544
50. Martín-García F, Papaleo E, Gomez-Puertas P et al (2015) Comparing molecular dynamics force fields in the essential subspace. PLoS One 10:e0121114
51. McCammon J, Gelin B, Karplus M (1977) Dynamics of folded proteins. Nature 267:585–590
52. Mereghetti P, Riccardi L, Brandsdal BO et al (2010) Near native-state conformational landscape of psychrophilic and mesophilic enzymes: probing the folding funnel model. J Phys Chem B 114:7609–7619
53. Mittermaier AK, Kay LE (2009) Observing biological dynamics at atomic resolution using NMR. Trends Biochem Sci 34:601–611
54. Nashine VC, Hammes-Schiffer S, Benkovic SJ (2010) Coupled motions in enzyme catalysis. Curr Opin Chem Biol 14:644–651
55. Nussinov R (2014) The significance of the 2013 Nobel Prize in Chemistry and the challenges ahead. PLoS Comput Biol 10:e1003423
56. Olufsen M, Smalås AO, Moe E, Brandsdal BO (2005) Increased flexibility as a strategy for cold adaptation: a comparative molecular dynamics study of cold-and warm-active uracil DNA glycosylase. J Biol Chem 280:18042–18048
57. Olufsen M, Brandsdal BO, Smalås AO (2007) Comparative unfolding studies of psychrophilic and mesophilic uracil DNA glycosylase: MD simulations show reduced thermal stability of the cold-adapted enzyme. J Mol Graph Model 26:124–134
58. Onuchic JN, Wolynes PG (2004) Theory of protein folding. Curr Opin Struct Biol 14:70–75
59. Palazzesi F, Barducci A, Tollinger M, Parrinello M (2013) The allosteric communication pathways in KIX domain of CBP. Proc Natl Acad Sci USA 110:14237–14242
60. Papaleo E, Fantucci P, De Gioia L (2005) Effects of calcium binding on structure and autolysis regulation in trypsins. A molecular dynamics investigation. J Chem Theory Comput 1:1286–1297
61. Papaleo E, Riccardi L, Villa C et al (2006) Flexibility and enzymatic cold-adaptation: a comparative molecular dynamics investigation of the elastase family. Biochim Biophys Acta 1764:1397–1406
62. Papaleo E, Olufsen M, De Gioia L, Brandsdal BO (2007) Optimization of electrostatics as a strategy for cold-adaptation: a case study of cold-and warm-active elastases. J Mol Graph Model 26:93–103
63. Papaleo E, Pasi M, Riccardi L et al (2008) Protein flexibility in psychrophilic and mesophilic trypsins. Evidence of evolutionary conservation of protein dynamics in trypsin-like serine-proteases. FEBS Lett 582:1008–1018
64. Papaleo E, Mereghetti P, Fantucci P, Grandori R, De Gioia L (2009) Free-energy landscape, principal component analysis, and structural clustering to identify representative conformations from molecular dynamics simulations: the myoglobin case. J Mol Graph Model 27:889–899
65. Papaleo E, Pasi M, Tiberti M, De Gioia L (2011a) Molecular dynamics of mesophilic-like mutants of a cold-adapted enzyme: insights into distal effects induced by the mutations. PLoS One 6:e24214
66. Papaleo E, Tiberti M, Invernizzi G et al (2011b) Molecular determinants of enzyme cold adaptation: comparative structural and computational studies of cold-and warm-adapted enzymes. Curr Protein Pept Sci 12:657–683
67. Papaleo E, Renzetti G, Tiberti M (2012) Mechanisms of intramolecular communication in a hyperthermophilic acylaminoacyl peptidase: a molecular dynamics investigation. PLoS One 7:e35686
68. Papaleo E, Renzetti G, Invernizzi G, Asgeirsson B (2013) Dynamics fingerprint and inherent asymmetric flexibility of a cold-adapted homodimeric enzyme. A case study of the Vibrio alkaline phosphatase. Biochim Biophys Acta 1830:2970–2980
69. Papaleo E, Parravicini F, Grandori R et al (2014a) Structural investigation of the cold-adapted acylaminoacyl peptidase from Sporosarcina psychrophila by atomistic simulations and bio-physical methods. Biochim Biophys Acta 1844:2203–2213
70. Papaleo E, Sutto L, Gervasio FL, Lindorff-Larsen K (2014b) Conformational changes and free energies in a proline isomerase. J Chem Theor Comput 10:4169–4174. doi:10.1021/ct500536r, 140820163733003
71. Parravicini F, Natalello A, Papaleo E et al (2013) Reciprocal influence of protein domains in the cold-adapted acyl aminoacyl peptidase from Sporosarcina psychrophila. PLoS One 8:e56254
72. Pasi M, Riccardi L, Fantucci P et al (2009) Dynamic properties of a psychrophilic alpha-amylase in comparison with a mesophilic homologue. J Phys Chem B 113:13585–13595
73. Piana S, Lindorff-Larsen K, Shaw DE (2013) Atomic-level description of ubiquitin folding. Proc Natl Acad Sci USA 110:5915–5920
74. Poland D (2001) Free energy distributions in proteins. Proteins 45:325–336
75. Ramli AN, Mahadi NM, Shamsir MS, Rabu A, Joyce-Tan KH, Murad AM, Illias RM (2012) Structural prediction of a novel chitinase from the psychrophilic glaciozyma antarctica Pl12 and an analysis of its structural properties and function. J Comput Aided Mol Des 26:947–961
76. Rapaport D (1998) The art of molecular dynamics simulation. Cambridge University Press, Cambridge, UK
77. Raval A, Piana S, Eastwood MP et al (2012) Refinement of protein structure homology models via long, all-atom molecular dynamics simulations. Proteins 80:2071–2079
78. Russell NJ (2000) Toward a molecular understanding of cold activity of enzymes from psychrophiles. Extremophiles 4:83–90
79. Siddiqui KS, Cavicchioli R (2006) Cold-adapted enzymes. Annu Rev Biochem 75:403–433
80. Sigtryggsdóttir AR, Papaleo E, Thorbjarnardóttir SH, Kristjánsson MM (2014) Flexibility of cold-and heat-adapted subtilisin-like serine proteinases evaluated with fluorescence quenching and molecular dynamics. Biochim Biophys Acta 1844:705–712
81. Smith JC, Roux B (2013) Eppur si muove! The 2013 Nobel Prize in Chemistry. Structure 21:2102–2105
82. Somero GN (2004) Adaptation of enzymes to temperature: searching for basic “strategies”. Comp Biochem Physiol B Biochem Mol Biol 139:321–333. doi:10.1016/j.cbpc.2004.05.003
83. Spiwok V, Lipovová P, Skálová T, Dusková J, Dohnálek J, Hasek J, Russell NJ, Králová B (2007) Cold-active enzymes studied by comparative molecular dynamics simulation. J Mol Model 13:485–497
84. Spiwok V, Sućur Z, Hošek P (2014) Enhanced sampling techniques in biomolecular simulations. Biotechnol Adv. doi:10.1016/j.biotechadv.2014.11.011
85. Struvay C, Feller G (2012) Optimization to low temperature activity in psychrophilic enzymes. Int J Mol Sci 13:11643–11665
86. Sutto L, Gervasio FL (2013) Effects of oncogenic mutations on the conformational free-energy landscape of EGFR kinase. Proc Natl Acad Sci 110:10616–10621. doi:10.1073/pnas.1221953110
87. Tehei M, Madern D, Franzetti B, Zaccai G (2005) Neutron scattering reveals the dynamic basis of protein adaptation to extreme temperature. J Biol Chem 280:40974–40979
88. Tiberti M, Papaleo E (2011) Dynamic properties of extremophilic subtilisin-like serine-proteases. J Struct Biol 174:69–83
89. Tronelli D, Maugini E, Bossa F, Pascarella S (2007) Structural adaptation to low temperatures— analysis of the subunit interface of oligomeric psychrophilic enzymes. FEBS J 274:4595–4608
90. Van den Bedem H, Fraser JS (2015) Integrative, dynamic structural biology at atomic resolution— it’s about time. Nat Methods 12:307–318
91. Van den Burg B (2003) Extremophiles as a source for novel enzymes. Curr Opin Microbiol 6:213–218
92. Van Gunsteren WF, Berendsen HJC (1990) Computer simulation of molecular dynamics: methodology, applications and perspective. Angew Chem Int Eng Ed 29:992–1023
93. Wintrode PL, Arnold FH (2000) Temperature adaptation of enzymes: lessons from laboratory evolution. Adv Protein Chem 55:161–225
94. Woldeyes RA, Sivak DA, Fraser JS (2014) E pluribus unum, no more: from one crystal, many conformations. Curr Opin Struct Biol 28C:56–62
95. Xie BB, Bian F, Chen XL, He HL, Guo J, Gao X, Zeng YX, Chen B, Zhou BC, Zhang YZ (2009) Cold adaptation of zinc metalloproteases in the thermolysin family from deep sea and arctic sea ice bacteria revealed by catalytic and structure properties and molecular dynamics: new insights into relationship between conformational flexibility and hydrogen bonding. J Biol Chem 284:9257–9269
96. Zhu T, Xiao X, Ji C, Zhang JZH (2013) A new quantum calibrated force field for zinc—protein complex. J Chem Theory Comput 9:1788–1798