Ions and inhibitors in the binding site of HIV protease

Comparison of Monte Carlo simulations and the linearized Poisson-Boltzmann theory

D. Boda, Mónika Valiskó, Douglas Henderson, Dirk Gillespie, Bob Eisenberg, Michael K. Gilson

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Proteins can be influenced strongly by the electrolyte in which they are dissolved, and we wish to model, understand, and ultimately control such ionic effects. Relatively detailed Monte Carlo (MC) ion simulations are needed to capture biologically important properties of ion channels, but a simpler treatment of ions, the linearized Poisson-Boltzmann (LPB) theory, is often used to model processes such as binding and folding, even in settings where the LPB theory is expected to be inaccurate. This study uses MC simulations to assess the reliability of the LPB theory for such a system, the constrained, anionic active site of HIV protease. We study the distributions of ions in and around the active site, as well as the energetics of displacing ions when a protease inhibitor is inserted into the active site. The LPB theory substantially underestimates the density of counterions in the active site when divalent cations are present. It also underestimates the energy cost of displacing these counterions, but the error is not consequential because the energy cost is less than kBT, according to the MC calculations. Thus, the LPB approach will often be suitable for studying energetics, but the more detailed MC approach is critical when ionic distributions and fluxes are at issue.

Original languageEnglish
Pages (from-to)1293-1306
Number of pages14
JournalBiophysical Journal
Volume96
Issue number4
DOIs
Publication statusPublished - Feb 18 2009

Fingerprint

HIV Protease
Catalytic Domain
Binding Sites
Ions
Costs and Cost Analysis
Divalent Cations
Protease Inhibitors
Ion Channels
Electrolytes
Proteins

ASJC Scopus subject areas

  • Biophysics

Cite this

Ions and inhibitors in the binding site of HIV protease : Comparison of Monte Carlo simulations and the linearized Poisson-Boltzmann theory. / Boda, D.; Valiskó, Mónika; Henderson, Douglas; Gillespie, Dirk; Eisenberg, Bob; Gilson, Michael K.

In: Biophysical Journal, Vol. 96, No. 4, 18.02.2009, p. 1293-1306.

Research output: Contribution to journalArticle

Boda, D. ; Valiskó, Mónika ; Henderson, Douglas ; Gillespie, Dirk ; Eisenberg, Bob ; Gilson, Michael K. / Ions and inhibitors in the binding site of HIV protease : Comparison of Monte Carlo simulations and the linearized Poisson-Boltzmann theory. In: Biophysical Journal. 2009 ; Vol. 96, No. 4. pp. 1293-1306.
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