Electric fields at the active site of an enzyme: Direct comparison of experiment with theory

Science

Volumn 313, Issue 5784, 2006, Pages 200-204

  Suydam, Ian T ^a   Snow, Christopher D ^a   Pande, Vijay S ^a   Boxer, Steven G ^a  

^a STANFORD UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

COMPUTER SIMULATION; ELECTRIC FIELDS; ELECTROSTATICS; MOLECULAR DYNAMICS; MOLECULAR VIBRATIONS; SPECTROSCOPIC ANALYSIS;

CALIBRATED NITRILE VIBRATION; FOLDED PROTEINS; NITRILE-CONTAINING INHIBITOR; STARK SHIFTS;

ENZYMES;

ALDEHYDE REDUCTASE; NITRILE;

COMPARATIVE STUDY; ELECTRIC FIELD; ENZYME; MUTATION; PROTEIN;

ARTICLE; CALCULATION; CALIBRATION; ELECTRIC FIELD; ELECTRICITY; ENZYME ACTIVE SITE; HUMAN; MATHEMATICAL ANALYSIS; MOLECULAR DYNAMICS; PRIORITY JOURNAL; PROTEIN FOLDING; QUANTITATIVE ANALYSIS; SIMULATION; SPECTROSCOPY; STRUCTURE ANALYSIS; VIBRATION; VIBRATIONAL SPECTROSCOPY;

ALDEHYDE REDUCTASE; BINDING SITES; CIRCULAR DICHROISM; COMPUTER SIMULATION; ELECTRICITY; ELECTROSTATICS; ENZYME INHIBITORS; HUMANS; MODELS, MOLECULAR; MUTATION; NITRILES; PROTEIN CONFORMATION; PROTEIN FOLDING; PROTEIN STRUCTURE, TERTIARY; SPECTROPHOTOMETRY, INFRARED; SPECTRUM ANALYSIS;

EID: 33746017658     PISSN: 00368075     EISSN: 10959203     Source Type: Journal    
DOI: 10.1126/science.1127159     Document Type: Article

References (30)

1. B. Honig, A. Nicholls, Science 268, 1144 (1995).
2. T. Simonson, Curr. Opin. Struct. Biol. 11, 243 (2001).
3. A. Warshel, A. Papazyan, Curr. Opin. Struct. Biol. 8, 211 (1998).
4. J. Villa, A. Warshel, J. Phys. Chem. B 105, 7887 (2001).
5. G. U. Bublitz, S. G. Boxer, Annu. Rev. Phys. Chem. 48, 213 (1997).
6. E. Oldfield, Annu. Rev. Phys. Chem. 53, 349 (2002).
7. E. S. Park, S. S. Andrews, R. B. Hu, S. G. Boxer, J. Phy. Chem. B 103, 9813 (1999).
8. S. S. Andrews, S. G. Boxer, J. Phys. Chem. A 104, 11853 (2000).
9. S. S. Andrews, S. G. Boxer, J. Phys. Chem. A 106, 469 (2002).
10. I. T. Suydam, S. G. Boxer, Biochemistry 42, 12050 (2003).
11. E. S. Park, S. G. Boxer, J. Phys. Chem. B 106, 5800 (2002).
12. J. R. Reimers, J. Zeng, N. S. Hush, J. Phys. Chem. 100, 1498 (1996).
13. H. Lehle et al., Biophys. J. 88, 1978 (2005).
14. K. Kirshenbaum, I. S. Carrico, D. A. Tirrell, ChemBioChem 3, 235 (2002).
15. Z. Getahun et al., J. Am. Chem. Soc. 125, 405 (2003).
16. S. K. Srivastava, K. V. Ramana, A. Bhatnagar, Endocr. Rev. 26, 380 (2005).
17. A. Podjarny, R. E. Cachau, T. Schneider, M. Van Zandt, A. Joachimiak, Cell. Mol. Life Sci. 61, 763 (2004).
18. M. C. Van Zandt et al., Bioorg. Med. Chem. 12, 5661 (2004).
19. N. Muzet, B. Guillot, C. Jelsch, E. Howard, C. Lecomte, Proc. Natl. Acad. Sci. U.S.A. 100, 8742 (2003).
20. E. I. Howard et al., Proteins Struct. Funct. Bioinform. 55, 792 (2004).
21. Materials and methods are available as supporting material on Science Online.
22. Single-letter abbreviations for the amino acid residues are as follows: A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, Ile; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; Q, Gln; R, Arg; S, Ser; T, Thr; V, Val; W, Trp; and Y, Tyr.
23. V. Lamour et al., Acta Crystallogr. 55, 721 (1999).
24. R. E. Georgescu, E. G. Alexov, M. R. Gunner, Biophys. J. 83, 1731 (2002).
25. M. K. Gilson, B. H. Honig, Biopolymers 25, 2097 (1986).
26. C. N. Schutz, A. Warshel, Proteins Struct. Funct. Genet. 44, 400 (2001).
27. C. D. Snow, E. J. Sorin, Y. M. Rhee, V. S. Pande, Annu. Rev. Biophys. Biomol. Struct. 34, 43 (2005).
28. 19F]tryptophan-labeled galactose binding protein to differences in electric field at each tryptophan position (29). That study calculated electric fields for a fluorine-substituted wild-type structure, whereas we wished to calculate fields for mutations for which structural information was unavailable. Our continuum solvent models are approximate in comparison to the Local Reaction Field method used in that study. However, distributed MD simulations allowed us to reach longer simulation times. These long time dynamics were required to converge the calculated fields for several of the mutants studied.
29. J. G. Pearson, E. Oldfield, F. S. Lee, A. Warshel, J. Am. Chem. Soc. 115, 6851 (1993).
30. We thank M. Van Zandt and co-workers for providing the inhibitor IDD743 and for many helpful comments, A. Podjarny for structural information used to model IDD743 binding, and A. Fafarman for electronic structure calculations used to parameterize electrostatics calculations and MD simulations. Supported by grants from the NIH, NSF Chemistry Division, and Howard Hughes Medical Institute predoctoral fellowship program (C.D.S.).