Computational Prediction of Allosteric Structural Changes by a Simple Mechanical   Model: Application to Hemoglobin T ßà R Transition

Chunyan Xu and Ivet Bahar       Biochemistry, 2002, submitted

Distribution of ms fluctuations driven by the global mode and the second slowest mode of motion

(a).Distribution of ms fluctuations driven by the global mode of motion. Maxima refer to flexible regions, and the minima to hinge sites. Note that compared with T, two minima at a36-45 and b87-102 disappear in the R form, suggesting a loosening or relaxation, and thereby an impediment in the mechanical function of the hinge sites. The dynamics of a- and b-subunits are very similar in the T form, while the dynamics are different in the R2 form.

(b).The hinge regions of the slowest mode correspond to the a₁b₂ interface.

(c).Second slowest mode shape.

(d).Hinge sites operative in the second slowest mode correspond to hinge sites at the a₁-b₁ and a₂-b₂ interfaces. 

Comparison of the first principle mode of R2 tetramer (part c) to that of a₁b₁ (part a) and a₁b₂ (part b) dimers.

The coordinates for the R2 tetramer, the a₁b₁ dimer or a₁b₂ dimer of R2 are used to calculate the mean-square fluctuation driven by the slowest mode. We can see that in the a₁b₁ dimer, the a-subunit dynamics is similar to the b-subunit dynamics while in the a₁b₂ dimer, the a-subunit dynamics is very different from the b-subunit dynamics, and the profiles a₁b₂ dimer and R tetramer are very similar, indicating that the global mode shape of the tetramer is predominantly controlled by that of the a₁b₂ (or a₂b₁) dimer.

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