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Biophys J. Aug 1994; 67(2): 548–559.
PMCID: PMC1225398

Molecular dynamics simulations of an enzyme surrounded by vacuum, water, or a hydrophobic solvent.

Abstract

We report on molecular dynamics simulations of a medium-sized protein, a lipase from Rhizomucor miehei, in vacuum, in water, and in a nonpolar solvent, methyl hexanoate. Depending on force field and solvent, the molecular dynamics structures obtained as averages over 150 ps had root-mean-square deviations in the range of 1.9 to 3.6 A from the crystal structure. The largest differences between the structures were in hydrogen bonding and exposed surface areas of the protein. The surface area increased in both solvents and became smaller in vacuum. The change of surface exposure varied greatly between different residues and occurred in accordance with the hydrophobicity of the residue and the nature of the solvent. The fluctuations of the atoms were largest in the external loops and agreed well with crystallographic temperature factors. Root-mean-square fluctuations were significantly smaller in the nonpolar solvents than they were in water, which is in accordance with the notion that proteins become more rigid in nonpolar solvents. In methyl hexanoate a partial opening of the lid covering the active site occurred, letting a methyl hexanoate molecule approach the active site.

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Selected References

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  • Bashford D, Gerwert K. Electrostatic calculations of the pKa values of ionizable groups in bacteriorhodopsin. J Mol Biol. 1992 Mar 20;224(2):473–486. [PubMed]
  • Bernstein FC, Koetzle TF, Williams GJ, Meyer EF, Jr, Brice MD, Rodgers JR, Kennard O, Shimanouchi T, Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol. 1977 May 25;112(3):535–542. [PubMed]
  • Brzozowski AM, Derewenda U, Derewenda ZS, Dodson GG, Lawson DM, Turkenburg JP, Bjorkling F, Huge-Jensen B, Patkar SA, Thim L. A model for interfacial activation in lipases from the structure of a fungal lipase-inhibitor complex. Nature. 1991 Jun 6;351(6326):491–494. [PubMed]
  • Fitzpatrick PA, Steinmetz AC, Ringe D, Klibanov AM. Enzyme crystal structure in a neat organic solvent. Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8653–8657. [PMC free article] [PubMed]
  • Komeiji Y, Uebayasi M, Someya J, Yamato I. A molecular dynamics study of solvent behavior around a protein. Proteins. 1993 Jul;16(3):268–277. [PubMed]
  • SARDA L, DESNUELLE P. Action de la lipase pancréatique sur les esters en émulsion. Biochim Biophys Acta. 1958 Dec;30(3):513–521. [PubMed]
  • Schrag JD, Li YG, Wu S, Cygler M. Ser-His-Glu triad forms the catalytic site of the lipase from Geotrichum candidum. Nature. 1991 Jun 27;351(6329):761–764. [PubMed]
  • van Tilbeurgh H, Sarda L, Verger R, Cambillau C. Structure of the pancreatic lipase-procolipase complex. Nature. 1992 Sep 10;359(6391):159–162. [PubMed]
  • Waks M. Proteins and peptides in water-restricted environments. Proteins. 1986 Sep;1(1):4–15. [PubMed]
  • Winkler FK, D'Arcy A, Hunziker W. Structure of human pancreatic lipase. Nature. 1990 Feb 22;343(6260):771–774. [PubMed]
  • Zaks A, Klibanov AM. Enzymatic catalysis in organic media at 100 degrees C. Science. 1984 Jun 15;224(4654):1249–1251. [PubMed]

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