Spontaneous quaternary and tertiary T-R transitions of human hemoglobin in molecular dynamics simulation

34Citations
Citations of this article
54Readers
Mendeley users who have this article in their library.

Abstract

We present molecular dynamics simulations of unliganded human hemoglobin (Hb) A under physiological conditions, starting from the R, R2, and T state. The simulations were carried out with protonated and deprotonated HC3 histidines His(β)146, and they sum up to a total length of 5.6μs. We observe spontaneous and reproducible T→R quaternary transitions of the Hb tetramer and tertiary transitions of the α and β subunits, as detected from principal component projections, from an RMSD measure, and from rigid body rotation analysis. The simulations reveal a marked asymmetry between the α and β subunits. Using the mutual information as correlation measure, we find that the β subunits are substantially more strongly linked to the quaternary transition than the α subunits. In addition, the tertiary populations of the α and β subunits differ substantially, with the β subunits showing a tendency towards R, and the α subunits showing a tendency towards T. Based on the simulation results, we present a transition pathway for coupled quaternary and tertiary transitions between the R and T conformations of Hb. © 2010 Hub et al.

Cite

CITATION STYLE

APA

Hub, J. S., Kubitzki, M. B., & de Groot, B. L. (2010). Spontaneous quaternary and tertiary T-R transitions of human hemoglobin in molecular dynamics simulation. PLoS Computational Biology, 6(5), 1–11. https://doi.org/10.1371/journal.pcbi.1000774

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free