1932

Abstract

Measurement of the electrostatic interactions that give rise to biological functions has been a longstanding challenge in biophysics. Advances in spectroscopic techniques over the past two decades have allowed for the direct measurement of electric fields in a wide variety of biological molecules and systems via the vibrational Stark effect (VSE). The frequency of the nitrile stretching oscillation has received much attention as an electric field reporter because of its sensitivity to electric fields and its occurrence in a relatively transparent region of the infrared spectrum. Despite these advantages and its wide use as a VSE probe, the nitrile stretching frequency is sensitive to hydrogen bonding in a way that complicates the straightforward relationship between measured frequency and environmental electric field. Here we highlight recent applications of nitrile VSE probes with an emphasis on experiments that have helped shape our understanding of the determinants of nitrile frequencies in both hydrogen bonding and nonhydrogen bonding environments.

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2018-04-20
2024-06-22
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Literature Cited

  1. Sheinerman FB, Honig B. 1.  2002. On the role of electrostatic interactions in the design of protein–protein interfaces. J. Mol. Biol. 318:1161–77 [Google Scholar]
  2. Rohs R, West SM, Sosinsky A, Liu P, Mann RS, Honig B. 2.  2009. The role of DNA shape in protein-DNA recognition. Nature 461:72681248–53 [Google Scholar]
  3. Gilson MK, Honig BH. 3.  1987. Calculation of electrostatic potentials in an enzyme active site. Nature 330:614384–86 [Google Scholar]
  4. Mulgrew-Nesbitt A, Diraviyam K, Wang J, Singh S, Murray P. 4.  et al. 2006. The role of electrostatics in protein–membrane interactions. Biochim. Biophys. Acta 1761:8812–26 [Google Scholar]
  5. Simonson T. 5.  2001. Macromolecular electrostatics: continuum models and their growing pains. Curr. Opin. Struct. Biol. 11:2243–52 [Google Scholar]
  6. Fogolari F, Brigo A, Molinari H. 6.  2002. The Poisson–Boltzmann equation for biomolecular electrostatics: a tool for structural biology. J. Mol. Recognit. 15:6377–92 [Google Scholar]
  7. Baker NA. 7.  2004. Poisson–Boltzmann methods for biomolecular electrostatics. Methods Enzymol 383:94–118 [Google Scholar]
  8. Nielsen JE, McCammon JA. 8.  2003. Calculating pKa values in enzyme active sites. Protein Sci 12:91894–901 [Google Scholar]
  9. Langsetmo K, Fuchs JA, Woodward C. 9.  1991. The conserved, buried aspartic acid in oxidized Escherichia coli thioredoxin has a pKa of. 7: .5. Its titration produces a related shift in global stability. Biochemistry 30:307603–9 [Google Scholar]
  10. Davoodi J, Wakarchuk WW, Campbell RL, Carey PR, Surewicz WK. 10.  1995. Abnormally high pKa of an active-site glutamic acid residue in Bacillus circulans xylanase. The role of electrostatic interactions. Eur. J. Biochem. 232:3839–43 [Google Scholar]
  11. Merz KM Jr. 11.  1991. Determination of pKas of ionizable groups in proteins: the pKa of Glu 7 and 35 in hen egg white lysozome and Glu 106 in human carbonic anhydrase II. J. Am. Chem. Soc. 113:3572–75 [Google Scholar]
  12. Alexov EG, Gunner MR. 12.  1999. Calculated protein and proton motions coupled to electron transfer: electron transfer from QA to QB in bacterial photosynthetic reaction centers. Biochemistry 38:268253–70 [Google Scholar]
  13. Popovic DM, Stuchebrukhov AA. 13.  2004. Electrostatic study of the proton pumping mechanism in bovine heart cytochrome C oxidase. J. Am. Chem. Soc. 126:61858–71 [Google Scholar]
  14. Elcock AH, Gabdoulline RR, Wade RC, McCammon JA. 14.  1999. Computer simulation of protein–protein association kinetics: acetylcholinesterase-fasciculin. J. Mol. Biol. 291:1149–62 [Google Scholar]
  15. Schreiber G, Fersht A. 15.  1996. Rapid, electrostatically assisted association of proteins. Nat. Struct. Biol. 3:5427–31 [Google Scholar]
  16. Dwyer JJ, Gittis AG, Karp DA, Lattman EE, Spencer DS. 16.  et al. 2000. High apparent dielectric constants in the interior of a protein reflect water penetration. Biophys. J. 79:31610–20 [Google Scholar]
  17. Isom DG, Castañeda CA, Cannon BR, García-Moreno EB. 17.  2011. Large shifts in pKa values of lysine residues buried inside a protein. PNAS 108:135260–65 [Google Scholar]
  18. Nielsen JE, Gunner MR, García-Moreno EB. 18.  2011. The pKa Cooperative: a collaborative effort to advance structure-based calculations of pKa values and electrostatic effects in proteins. Proteins 79:123249–59 [Google Scholar]
  19. Fried SD, Boxer SG. 19.  2015. Measuring electric fields and noncovalent interactions using the vibrational stark effect. Acc. Chem. Res. 48:4998–1006 [Google Scholar]
  20. Fried SD, Boxer SG. 20.  2017. Electric fields and enzyme catalysis. Annu. Rev. Biochem. 86:1387–415 [Google Scholar]
  21. de Dios A, Pearson J, Oldfield E. 21.  1993. Secondary and tertiary structural effects on protein NMR chemical shifts: an ab initio approach. Science 260:51131491–96 [Google Scholar]
  22. Oldfield E. 22.  1995. Chemical shifts and 3-dimensional protein structures. J. Biomol. NMR 5:3217–25 [Google Scholar]
  23. Boxer SG. 23.  2009. Stark realities. J. Phys. Chem. B 113:102972–83 [Google Scholar]
  24. Ma J, Pazos IM, Zhang W, Culik RM, Gai F. 24.  2015. Site-specific infrared probes of proteins. Annu. Rev. Phys. Chem. 66:1357–77 [Google Scholar]
  25. Adhikary R, Zimmermann J, Romesberg FE. 25.  2017. Transparent window vibrational probes for the characterization of proteins with high structural and temporal resolution. Chem. Rev. 117:31927–69 [Google Scholar]
  26. Błasiak B, Londergan CH, Webb LJ, Cho M. 26.  2017. Vibrational probes: from small molecule solvatochromism theory and experiments to applications in complex systems. Acc. Chem. Res. 50:4968–76 [Google Scholar]
  27. Stark J. 27.  1913. Observation of the separation of spectral lines by an electric field. Nature 92:2301401 [Google Scholar]
  28. Lockhart DJ, Boxer SG. 28.  1987. Magnitude and direction of the change in dipole moment associated with excitation of the primary electron donor in Rhodopseudomonas sphaeroides reaction centers. Biochemistry 26:3664–68 [Google Scholar]
  29. Lockhart DJ, Boxer SG. 29.  1988. Stark effect spectroscopy of Rhodobacter sphaeroides and Rhodopseudomonas viridis reaction centers. PNAS 85:1107–11 [Google Scholar]
  30. Lockhart DJ, Kirmaier C, Holten D, Boxer SG. 30.  1990. Electric field effects on the initial electron-transfer kinetics in bacterial photosynthetic reaction centers. J. Phys. Chem. 94:186987–95 [Google Scholar]
  31. Steffen MA, Lao K, Boxer SG. 31.  1994. Dielectric asymmetry in the photosynthetic reaction center. Science 264:5160810–16 [Google Scholar]
  32. Chattoraj M, King BA, Bublitz GU, Boxer SG. 32.  1996. Ultra-fast excited state dynamics in green fluorescent protein: multiple states and proton transfer. PNAS 93:168362–67 [Google Scholar]
  33. Bublitz G, King BA, Boxer SG. 33.  1998. Electronic structure of the chromophore in green fluorescent protein (GFP). J. Am. Chem. Soc. 120:369370–71 [Google Scholar]
  34. Oh DH, Boxer SG. 34.  1990. Electrochromism in the near-infrared absorption spectra of bridged ruthenium mixed-valence complexes. J. Am. Chem. Soc. 112:178161–63 [Google Scholar]
  35. Oh DH, Sano M, Boxer SG. 35.  1991. Electroabsorption (Stark effect) spectroscopy of mono- and biruthenium charge-transfer complexes: measurements of changes in dipole moments and other electrooptic properties. J. Am. Chem. Soc. 113:186880–90 [Google Scholar]
  36. Pierce DW, Boxer SG. 36.  1995. Stark effect spectroscopy of tryptophan. Biophys. J. 68:41583–91 [Google Scholar]
  37. Franzen S, Moore LJ, Woodruff WH, Boxer SG. 37.  1999. Stark-effect spectroscopy of the heme charge-transfer bands of deoxymyoglobin. J. Phys. Chem. B 103:3070–72 [Google Scholar]
  38. Park ES, Thomas MR, Boxer SG. 38.  2000. Vibrational Stark spectroscopy of NO bound to heme: effects of protein electrostatic fields on the NO stretch frequency. J. Am. Chem. Soc. 122:4912297–303 [Google Scholar]
  39. Park ES, Boxer SG. 39.  2002. Origins of the sensitivity of molecular vibrations to electric fields: carbonyl and nitrosyl stretches in model compounds and proteins. J. Phys. Chem. B 106:225800–6 [Google Scholar]
  40. Fried SD, Bagchi S, Boxer SG. 40.  2013. Measuring electrostatic fields in both hydrogen bonding and non-hydrogen bonding environments using carbonyl vibrational probes. J. Am. Chem. Soc. 135:11181–92 [Google Scholar]
  41. Andrews SS, Boxer SG. 41.  2000. Vibrational Stark effects of nitriles I. Methods and experimental results. J. Phys. Chem. A 104:5111853–63 [Google Scholar]
  42. Andrews SS, Boxer SG. 42.  2002. Vibrational Stark effects of nitriles II. Physical origins of Stark effects from experiment and perturbation models. J. Phys. Chem. A 106:3469–77 [Google Scholar]
  43. Webb LJ, Boxer SG. 43.  2008. Electrostatic fields near the active site of human aldose reductase: 1. New inhibitors and vibrational stark effect measurements. Biochemistry 47:61588–98 [Google Scholar]
  44. Suydam IT, Boxer SG. 44.  2003. Vibrational Stark effects calibrate the sensitivity of vibrational probes for electric fields in proteins. Biochemistry 42:4112050–55 [Google Scholar]
  45. Suydam IT, Snow CD, Pande VS, Boxer SG. 45.  2006. Electric fields at the active site of an enzyme: direct comparison of experiment with theory. Science 313:200–4 [Google Scholar]
  46. Russell ST, Warshel A. 46.  1985. Calculations of electrostatic energies in proteins. The energetics of ionized groups in bovine pancreatic trypsin inhibitor. J. Mol. Biol. 185:389–404 [Google Scholar]
  47. Walker DM, Hayes EC, Webb LJ. 47.  2013. Vibrational Stark effect spectroscopy reveals complementary electrostatic fields created by protein–protein binding at the interface of Ras and Ral. Phys. Chem. Chem. Phys. 15:2912241–52 [Google Scholar]
  48. Walker DM, Wang R, Webb LJ. 48.  2014. Conserved electrostatic fields at the Ras-effector interface measured through vibrational Stark effect spectroscopy explain the difference in tilt angle in the Ras binding domains of Raf and RalGDS. Phys. Chem. Chem. Phys. 16:3720047–60 [Google Scholar]
  49. Stafford AJ, Walker DM, Webb LJ. 49.  2012. Electrostatic effects of mutations of Ras glutamine 61 measured using vibrational spectroscopy of a thiocyanate probe. Biochemistry 51:132757–67 [Google Scholar]
  50. Fafarman AT, Boxer SG. 50.  2010. Nitrile bonds as infrared probes of electrostatics in ribonuclease S. J. Phys. Chem. B 114:4213536–44 [Google Scholar]
  51. Fafarman AT, Sigala PA, Schwans JP, Fenn TD, Herschlag D, Boxer SG. 51.  2012. Quantitative, directional measurement of electric field heterogeneity in the active site of ketosteroid isomerase. PNAS 109:6E299–308 [Google Scholar]
  52. Fried SD, Bagchi S, Boxer SG. 52.  2014. Extreme electric fields power catalysis in the active site of ketosteroid isomerase. Science 346:62161510–14 [Google Scholar]
  53. Wang L, Brock A, Herberich B, Schultz PG. 53.  2001. Expanding the genetic code of Escherichia coli. . Science 292:5516498–500 [Google Scholar]
  54. Schultz KC, Supekova L, Ryu Y, Xie J, Perera R, Schultz PG. 54.  2006. A genetically encoded infrared probe. J. Am. Chem. Soc. 128:4313984–85 [Google Scholar]
  55. Hammill JT, Miyake-Stoner S, Hazen JL, Jackson JC, Mehl RA. 55.  2007. Preparation of site-specifically labeled fluorinated proteins for 19F-NMR structural characterization. Nat. Protoc. 2:102601–7 [Google Scholar]
  56. Fafarman AT, Webb LJ, Chuang JI, Boxer SG. 56.  2006. Site-specific conversion of cysteine thiols into thiocyanate creates an IR probe for electric fields in proteins. J. Am. Chem. Soc. 128:4113356–57 [Google Scholar]
  57. Tsien RY. 57.  1998. The green fluorescent protein. Annu. Rev. Biochem. 67:509–44 [Google Scholar]
  58. Bagchi S, Fried SD, Boxer SG. 58.  2012. A solvatochromic model calibrates nitriles’ vibrational frequencies to electrostatic fields. J. Am. Chem. Soc. 134:10373–76 [Google Scholar]
  59. Lindquist BA, Furse KE, Corcelli SA. 59.  2009. Nitrile groups as vibrational probes of biomolecular structure and dynamics: an overview. Phys. Chem. Chem. Phys. 11:378119–32 [Google Scholar]
  60. Völler J-S, Biava H, Hildebrandt P, Budisa N. 60.  2016. An expanded genetic code for probing the role of electrostatics in enzyme catalysis by vibrational Stark spectroscopy. Biochim. Biophys. Acta 1861:11B3053–59 [Google Scholar]
  61. Pace EL, Noe LJ. 61.  1968. Infrared spectra of acetonitrile and acetonitrile-d3. J. Chem. Phys. 49:125317–25 [Google Scholar]
  62. Reimers J, Zeng J, Hush N. 62.  1996. Vibrational Stark spectroscopy 2. Application to the CN stretch in HCN and acetonitrile. J. Phys. Chem. 100:51498–504 [Google Scholar]
  63. Nyquist RA. 63.  1990. Solvent-induced nitrile frequency shifts: acetonitrile and benzonitrile. Appl. Spectrosc. 44:1405–7 [Google Scholar]
  64. Fawcett WR, Liu G, Kessler TE. 64.  1993. Solvent-induced frequency shifts in the infrared spectrum of acetonitrile in organic solvents. J. Phys. Chem. 97:379293–98 [Google Scholar]
  65. Reimers JR, Hall LE. 65.  1999. The solvation of acetonitrile. J. Am. Chem. Soc. 121:153730–44 [Google Scholar]
  66. McCoy S, Caughey WS. 66.  1970. Infrared studies of azido, cyano, and other derivatives of metmyoglobin, methemoglobin, and hemins. Biochemistry 9:122387–93 [Google Scholar]
  67. Yoshikawa S, O'Keeffe DH, Caughey WS. 67.  1985. Investigations of cyanide as an infrared probe of hemeprotein ligand binding sites. J. Biol. Chem. 260:63518–28 [Google Scholar]
  68. Getahun Z, Huang CY, Wang T, De León B, DeGrado WF, Gai F. 68.  2003. Using nitrile-derivatized amino acids as infrared probes of local environment. J. Am. Chem. Soc. 125:2405–11 [Google Scholar]
  69. Merrifield RB. 69.  1963. Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. J. Am. Chem. Soc. 85:142149–54 [Google Scholar]
  70. Aprilakis KN, Taskent H, Raleigh DP. 70.  2007. Use of the novel fluorescent amino acid p-cyanophenylalanine offers a direct probe of hydrophobic core formation during the folding of the N-terminal domain of the ribosomal protein L9 and provides evidence for two-state folding. Biochemistry 46:4312308–13 [Google Scholar]
  71. Getahun Z, Huang CY, Wang T, De León B, Degrado WF, Gai F. 71.  2003. Using nitrile-derivatized amino acids as infrared probes of local environment. J. Am. Chem. Soc. 125:405–11 [Google Scholar]
  72. Adhikary R, Zimmermann J, Dawson PE, Romesberg FE. 72.  2014. IR probes of protein microenvironments: utility and potential for perturbation. ChemPhysChem 15:5849–53 [Google Scholar]
  73. Adhikary R, Zimmermann J, Dawson PE, Romesberg FE. 73.  2015. Temperature dependence of CN and SCN IR absorptions facilitates their interpretation and use as probes of proteins. Anal. Chem. 87:2211561–67 [Google Scholar]
  74. Hu W, Webb LJ. 74.  2011. Direct measurement of the membrane dipole field in bicelles using vibrational stark effect spectroscopy. J. Phys. Chem. Lett. 2:151925–30 [Google Scholar]
  75. Shrestha R, Cardenas AE, Elber R, Webb LJ. 75.  2015. Measurement of the membrane dipole electric field in DMPC vesicles using vibrational shifts of p-cyanophenylalanine and molecular dynamics simulations. J. Phys. Chem. B 119:72869–76 [Google Scholar]
  76. Ellman GL. 76.  1958. A colorimetric method for determining low concentrations of mercaptans. Arch. Biochem. Biophys. 74:443–45 [Google Scholar]
  77. Noren C, Anthony-Cahill S, Griffith M, Schultz P. 77.  1989. A general method for site-specific incorporation of unnatural amino acids into proteins. Science 244:4901182–88 [Google Scholar]
  78. Wang L, Xie J, Schultz PG. 78.  2006. Expanding the genetic code. Annu. Rev. Biophys. Biomol. Struct. 35:1225–49 [Google Scholar]
  79. Miyake-Stoner SJ, Refakis CA, Hammill JT, Lusic H, Hazen JL. 79.  et al. 2010. Generating permissive site-specific unnatural aminoacyl-tRNA synthetases. Biochemistry 49:81667–77 [Google Scholar]
  80. Maienschein-Cline MG, Londergan CH. 80.  2007. The CN stretching band of aliphatic thiocyanate is sensitive to solvent dynamics and specific solvation. J. Phys. Chem. A 111:4010020–25 [Google Scholar]
  81. Choi J-H, Oh K-I, Lee H, Lee C, Cho M. 81.  2008. Nitrile and thiocyanate IR probes: quantum chemistry calculation studies and multivariate least-square fitting analysis. J. Chem. Phys. 128:13134506 [Google Scholar]
  82. Fafarman AT, Sigala PA, Herschlag D, Boxer SG. 82.  2010. Decomposition of vibrational shifts of nitriles into electrostatic and hydrogen-bonding effects. J. Am. Chem. Soc. 132:3712811–13 [Google Scholar]
  83. Liu CT, Layfield JP, Stewart RJ, French JB, Hanoian P. 83.  et al. 2014. Probing the electrostatics of active site microenvironments along the catalytic cycle for Escherichia coli dihydrofolate reductase. J. Am. Chem. Soc. 136:2910349–60 [Google Scholar]
  84. Deb P, Haldar T, Kashid SM, Banerjee S, Chakrabarty S, Bagchi S. 84.  2016. Correlating nitrile IR frequencies to local electrostatics quantifies noncovalent interactions of peptides and proteins. J. Phys. Chem. B 120:174034–46 [Google Scholar]
  85. Slocum JD, Webb LJ. 85.  2016. Nitrile probes of electric field agree with independently measured fields in green fluorescent protein even in the presence of hydrogen bonding. J. Am. Chem. Soc. 138:206561–70 [Google Scholar]
  86. Haldar T, Kashid SM, Deb P, Kesh S, Bagchi S. 86.  2016. Pick and choose the spectroscopic method to calibrate the local electric field inside proteins. J. Phys. Chem. Lett. 7:132456–60 [Google Scholar]
  87. Lide DR. 87.  2009. CRC Handbook of Chemistry and Physics Boca Raton, FL: CRC Press. , 90th ed.. [Google Scholar]
  88. Dippel AB, Olenginski GM, Maurici N, Liskov MT, Brewer SH, Phillips-Piro CM. 88.  2016. Probing the effectiveness of spectroscopic reporter unnatural amino acids: a structural study. Acta Crystallogr. D 72:1121–30 [Google Scholar]
  89. Ragain CM, Newberry RW, Ritchie AW, Webb LJ. 89.  2012. Role of electrostatics in differential binding of RalGDS to Rap mutations E30D and K31E investigated by vibrational spectroscopy of thiocyanate probes. J. Phys. Chem. B 116:319326–36 [Google Scholar]
  90. Ritchie AW, Webb LJ. 90.  2013. Optimizing electrostatic field calculations with the Adaptive Poisson–Boltzmann Solver to predict electric fields at protein-protein interfaces. I: Sampling and focusing. J. Phys. Chem. B 117:3911473–89 [Google Scholar]
  91. Ritchie AW, Webb LJ. 91.  2014. Optimizing electrostatic field calculations with the Adaptive Poisson–Boltzmann Solver to predict electric fields at protein-protein interfaces. II: Explicit near-probe and hydrogen bonding water molecules. J. Phys. Chem. B 118:287692–702 [Google Scholar]
  92. Slocum JD, First JT, Webb LJ. 92.  2017. Orthogonal electric field measurements near the green fluorescent protein fluorophore through Stark spectroscopy and pKa shifts provide a unique benchmark for electrostatics models. J. Phys. Chem. B 121:286799–812 [Google Scholar]
  93. Garrington TP, Johnson GL. 93.  1999. Organization and regulation of mitogen-activated protein kinase signaling pathways. Curr. Opin. Cell Biol. 11:2211–18 [Google Scholar]
  94. Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH. 94.  et al. 2005. A human protein–protein interaction network: a resource for annotating the proteome. Cell 122:6957–68 [Google Scholar]
  95. Cox AD, Der CJ. 95.  2003. The dark side of Ras: regulation of apoptosis. Oncogene 22:568999–9006 [Google Scholar]
  96. Downward J. 96.  2003. Targeting RAS signalling pathways in cancer therapy. Nat. Rev. Cancer 3:111–22 [Google Scholar]
  97. Stafford AJ, Ensign DL, Webb LJ. 97.  2010. Vibrational Stark effect spectroscopy at the interface of Ras and Rap1A bound to the Ras binding domain of RalGDS reveals an electrostatic mechanism for protein–protein interaction. J. Phys. Chem. B 114:4615331–44 [Google Scholar]
  98. Warshel A. 98.  1978. Energetics of enzyme catalysis. PNAS 75:115250–54 [Google Scholar]
  99. Warshel A, Sharma PK, Kato M, Xiang Y, Liu H, Olsson MHM. 99.  2006. Electrostatic basis for enzyme catalysis. Chem. Rev. 106:83210–35 [Google Scholar]
  100. Benkovic SJ. 100.  2003. A perspective on enzyme catalysis. Science 301:56371196–202 [Google Scholar]
  101. Honig B, Hubbell W, Flewelling R. 101.  1986. Electrostatic interactions in membranes and proteins. Annu. Rev. Biophys. Biophys. Chem. 15:163–93 [Google Scholar]
  102. Clarke R. 102.  2001. The dipole potential of phospholipid membranes and methods for its detection. Adv. Colloid Interface Sci. 89:90263–81 [Google Scholar]
  103. Gross E, Bedlack R, Loew L. 103.  1994. Dual-wavelength ratiometric fluorescence measurement of the membrane dipole potential. Biophys. J. 67:208–16 [Google Scholar]
  104. Shrestha R, Anderson CM, Cardenas AE, Elber R, Webb LJ. 104.  2017. Direct measurement of the effect of cholesterol and 6-ketocholestanol on membrane dipole field using vibrational Stark effect spectroscopy coupled with molecular dynamics simulations. J. Phys. Chem. B 121:153424–36 [Google Scholar]
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