Electrostatic field around cytochrome c: Theory and energy transfer experiment

Scott H. Northrup, Theodore G. Wensel, Claude F. Meares, John J. Wendoloski, James B. Matthew

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Energy transfer in the "rapid diffusion" limit from electronically excited terbium(III) chelates in three different charge states to horse heart ferricytochrome c was measured as a function of ionic strength. Theoretical rate constants calculated by numerical integration of the Forster integral (containing the Poisson-Boltzmann-generated protein electrostatic potential) were compared with the experimental data to evaluate the accuracy of protein electrostatic field calculations at the protein/solvent interface. Two dielectric formalism were used: a simple coulombic/Debye-Hückel procedure and a finite difference method [Warwicker, J. & Watson, H. C. (1982) J. Mol. Biol. 157, 671-679] that accounts for the low-dielectric protein interior and the irregular protein/solvent boundary. Good agreement with experiment was obtained and the ionic-strength dependence of the reaction was successfully reproduced. The sensitivity of theoretical rate constants to the choices of effective donor sphere size and the energy transfer distance criterion was analyzed. Electrostatic potential and rate-constant calculations were carried out on sets of structures collected along two molecular dynamics trajectories of cytochrome c. Protein conformational fluctuation were shown to produce large variations in the calculated energy transfer rate constant. We conclude that protein fluctuations and the resulting transient structures can play significant roles in biological or catalytic activities that are not apparent from examination of a static structure. For calculatint protein electrostatics, large-scale low-frequency conformational fluctuations, such as charged side-chain reorientation, are established to be as important as the computational method for incorporating dielectric boundary effects.

Original languageEnglish (US)
Pages (from-to)9503-9507
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number23
StatePublished - 1990

Keywords

  • Bimolecular rate
  • Fluorescence
  • Molecular dynamics
  • Poisson-Boltzmann equation
  • Protein

ASJC Scopus subject areas

  • Genetics
  • General

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