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Valid molecular dynamics simulations of human hemoglobin require a surprisingly large box size.
Journal article

Valid molecular dynamics simulations of human hemoglobin require a surprisingly large box size.

  • El Hage K Department of Chemistry, University of Basel, Basel, Switzerland.
  • Hédin F Department of Chemistry, University of Basel, Basel, Switzerland.
  • Gupta PK Department of Chemistry, University of Basel, Basel, Switzerland.
  • Meuwly M Department of Chemistry, University of Basel, Basel, Switzerland.
  • Karplus M Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, United States.
  • 2018-07-13
Published in:
  • eLife. - 2018
diffusion constant
hemoglobin
hydrophobic effect
molecular biophysics
molecular dynamics
none
simulation box size
structural biology
Hemoglobins
Humans
Hydrophobic and Hydrophilic Interactions
Molecular Dynamics Simulation
Protein Multimerization
Protein Stability
Protein Structure, Quaternary
Solvents
English Recent molecular dynamics (MD) simulations of human hemoglobin (Hb) give results in disagreement with experiment. Although it is known that the unliganded (T[Formula: see text]) and liganded (R[Formula: see text]) tetramers are stable in solution, the published MD simulations of T[Formula: see text] undergo a rapid quaternary transition to an R-like structure. We show that T[Formula: see text] is stable only when the periodic solvent box contains ten times more water molecules than the standard size for such simulations. The results suggest that such a large box is required for the hydrophobic effect, which stabilizes the T[Formula: see text] tetramer, to be manifested. Even in the largest box, T[Formula: see text] is not stable unless His146 is protonated, providing an atomistic validation of the Perutz model. The possibility that extra large boxes are required to obtain meaningful results will have to be considered in evaluating existing and future simulations of a wide range of systems.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/53905
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