Molecular dynamics simulation and MM-PBSA calculations of sickle cell hemoglobin in dimer form with Val, Trp, or Phe at the lateral contact

Abroshan, H ; Sharif University of Technology

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  1. Type of Document: Article
  2. DOI: 10.1002/poc.1679
  3. Abstract:
  4. As the delay time and hence nuclei formation play a crucial role in the pathophysiology of sickle cell disease, MD simulation and molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) calculations have been performed on three systems of hemoglobin; namely dimer of hemoglobin with valine (Hb S), tryptophan (Hbβ6W), and phenylalanine (Hbβ6F) at β6 position. The structural changes due to these aromatic substitutions are investigated. It is shown that β subunits have significant impact on the differences between a dimer and other crystal structures. Transition from a dimer to polymer for Hb S system affects the donor molecule more than that of the acceptor. In the case of donor and acceptor subunits, the RMSD values are ordered as Hbβ6F > Hbβ6W > Hb S which predicts a larger deviation for the Hbβ6F dimer. It is shown that the formation of stable dimers is in the order of Hbβ6F>Hb S > Hb|i6W, but contribution of the β6 residue in HbβW is more than two other systems. This study shows that the interaction of β6 residue in Hb S is mostly van der Waals type, but in two other systems the electrostatic interaction is also noticeable, especially in the case of Hbβ6W in which the hydrogen bond plays an important role in the association of monomers. Trp and Phe also have a stabilizing van der Waals interaction with a hydrophobic pocket composed of 1 β2-10Ala, 1β2-125Pro, 1β2-126Val, and 1β2-129Ala. Our survey shows that the role of 2β1-85Phe is very important only in the nucleus formation of Hb S, but not for the subsequent processes
  5. Keywords:
  6. Protein polymerization ; Sickle cell hemoglobin ; Aromatic substitutions ; Delay Time ; Donor and acceptor ; Donor molecules ; Electrostatic interactions ; Hydrophobic pockets ; Lateral contact ; MD simulation ; Molecular disease ; Molecular dynamics simulations ; Nuclei formation ; Pathophysiology ; Poisson-Boltzmann ; Protein-protein interaction ; S-systems ; Sickle cell ; Sickle cell disease ; Significant impacts ; Structural change ; Surface area ; Three systems ; Van der waals ; Van der Waals interactions ; Amino acids ; Association reactions ; Automobile exhibitions ; Hemoglobin ; Hydrogen ; Hydrogen bonds ; Molecular mechanics ; Oligomers ; Polymerization ; Polymers ; Van der Waals forces ; Molecular dynamics
  7. Source: Journal of Physical Organic Chemistry ; Volume 23, Issue 9 , March , 2010 , Pages 866-877 ; 08943230 (ISSN)
  8. URL: http://onlinelibrary.wiley.com/doi/10.1002/poc.1679/abstract