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. 1994 Aug 30;91(18):8715–8718. doi: 10.1073/pnas.91.18.8715

Atomic-level accuracy in simulations of large protein crystals.

D M York 1, A Wlodawer 1, L G Pedersen 1, T A Darden 1
PMCID: PMC44677  PMID: 7521533

Abstract

Proper treatment of long-range Coulombic forces presents a major obstacle to providing realistic molecular dynamics simulations of macromolecules. Traditional approximations made to lessen computational cost ultimately lead to unrealistic behavior. The particle mesh Ewald method accommodates long-range Coulombic forces accurately and efficiently by use of fast Fourier transform techniques. We report a 1-ns simulation of bovine pancreatic trypsin inhibitor in a crystal unit cell using the particle mesh Ewald methodology. We find an rms backbone deviation from the x-ray structure (0.33 A) that is lower than that observed between bovine pancreatic trypsin inhibitor in different crystal forms and much lower than those of previous simulations. These results bridge the gap between structures obtained from molecular simulation and those from experiment.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berendsen H. J., Van Gunsteren W. F., Zwinderman H. R., Geurtsen R. G. Simulations of proteins in water. Ann N Y Acad Sci. 1986;482:269–286. doi: 10.1111/j.1749-6632.1986.tb20961.x. [DOI] [PubMed] [Google Scholar]
  2. Berndt K. D., Güntert P., Orbons L. P., Wüthrich K. Determination of a high-quality nuclear magnetic resonance solution structure of the bovine pancreatic trypsin inhibitor and comparison with three crystal structures. J Mol Biol. 1992 Oct 5;227(3):757–775. doi: 10.1016/0022-2836(92)90222-6. [DOI] [PubMed] [Google Scholar]
  3. Blake G. M., Fogelman I. Recent advances in bone densitometry. Eur J Nucl Med. 1993 Sep;20(9):735–737. doi: 10.1007/BF00180901. [DOI] [PubMed] [Google Scholar]
  4. Daggett V., Levitt M. Realistic simulations of native-protein dynamics in solution and beyond. Annu Rev Biophys Biomol Struct. 1993;22:353–380. doi: 10.1146/annurev.bb.22.060193.002033. [DOI] [PubMed] [Google Scholar]
  5. Heiner A. P., Berendsen H. J., van Gunsteren W. F. MD simulation of subtilisin BPN' in a crystal environment. Proteins. 1992 Dec;14(4):451–464. doi: 10.1002/prot.340140406. [DOI] [PubMed] [Google Scholar]
  6. Housset D., Kim K. S., Fuchs J., Woodward C., Wlodawer A. Crystal structure of a Y35G mutant of bovine pancreatic trypsin inhibitor. J Mol Biol. 1991 Aug 5;220(3):757–770. doi: 10.1016/0022-2836(91)90115-m. [DOI] [PubMed] [Google Scholar]
  7. Kabsch W., Sander C. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers. 1983 Dec;22(12):2577–2637. doi: 10.1002/bip.360221211. [DOI] [PubMed] [Google Scholar]
  8. Kitson D. H., Avbelj F., Moult J., Nguyen D. T., Mertz J. E., Hadzi D., Hagler A. T. On achieving better than 1-A accuracy in a simulation of a large protein: Streptomyces griseus protease A. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8920–8924. doi: 10.1073/pnas.90.19.8920. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Levitt M., Perutz M. F. Aromatic rings act as hydrogen bond acceptors. J Mol Biol. 1988 Jun 20;201(4):751–754. doi: 10.1016/0022-2836(88)90471-8. [DOI] [PubMed] [Google Scholar]
  10. Lybrand T. P., McCammon J. A., Wipff G. Theoretical calculation of relative binding affinity in host-guest systems. Proc Natl Acad Sci U S A. 1986 Feb;83(4):833–835. doi: 10.1073/pnas.83.4.833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Petsko G. A., Ringe D. Fluctuations in protein structure from X-ray diffraction. Annu Rev Biophys Bioeng. 1984;13:331–371. doi: 10.1146/annurev.bb.13.060184.001555. [DOI] [PubMed] [Google Scholar]
  12. Schreiber H., Steinhauser O. Cutoff size does strongly influence molecular dynamics results on solvated polypeptides. Biochemistry. 1992 Jun 30;31(25):5856–5860. doi: 10.1021/bi00140a022. [DOI] [PubMed] [Google Scholar]
  13. Wlodawer A., Deisenhofer J., Huber R. Comparison of two highly refined structures of bovine pancreatic trypsin inhibitor. J Mol Biol. 1987 Jan 5;193(1):145–156. doi: 10.1016/0022-2836(87)90633-4. [DOI] [PubMed] [Google Scholar]
  14. Wlodawer A., Nachman J., Gilliland G. L., Gallagher W., Woodward C. Structure of form III crystals of bovine pancreatic trypsin inhibitor. J Mol Biol. 1987 Dec 5;198(3):469–480. doi: 10.1016/0022-2836(87)90294-4. [DOI] [PubMed] [Google Scholar]
  15. Wlodawer A., Walter J., Huber R., Sjölin L. Structure of bovine pancreatic trypsin inhibitor. Results of joint neutron and X-ray refinement of crystal form II. J Mol Biol. 1984 Dec 5;180(2):301–329. doi: 10.1016/s0022-2836(84)80006-6. [DOI] [PubMed] [Google Scholar]
  16. Yang A. S., Gunner M. R., Sampogna R., Sharp K., Honig B. On the calculation of pKas in proteins. Proteins. 1993 Mar;15(3):252–265. doi: 10.1002/prot.340150304. [DOI] [PubMed] [Google Scholar]
  17. York D. M., Darden T. A., Pedersen L. G., Anderson M. W. Molecular dynamics simulation of HIV-1 protease in a crystalline environment and in solution. Biochemistry. 1993 Feb 16;32(6):1443–1453. doi: 10.1021/bi00057a007. [DOI] [PubMed] [Google Scholar]
  18. van Gunsteren W. F., Berendsen H. J., Hermans J., Hol W. G., Postma J. P. Computer simulation of the dynamics of hydrated protein crystals and its comparison with x-ray data. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4315–4319. doi: 10.1073/pnas.80.14.4315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. van Gunsteren W. F., Karplus M. Protein dynamics in solution and in a crystalline environment: a molecular dynamics study. Biochemistry. 1982 May 11;21(10):2259–2274. doi: 10.1021/bi00539a001. [DOI] [PubMed] [Google Scholar]

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