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

 CONCLUSION:

1). In this study, we demonstrate that a simple elastic network model, GNM/ANM, can predict the most probable reconfigurations of Hb, i.e. the transition between the T and R2 forms. Numerous liganded and unliganded Hb revealed a number of structures that fall in between T and R2. Our studies tie the global motion of Hb directly to this functional conformational transition.

2). Numerous mutational and spectroscopic studies have shown that the hydrogen bond and salt bridge formation at the a₁b₂ interface are key to the allosteric activity of Hb. Without knowledge of any chemical and biological data on Hb function, using structural (purely geometric) information alone, we show that the hinge center for the most coordinated motion of Hb corresponds to the switch region at the a₁b₂ interface.

3). We identify a number of other interactions at the a₁-b₁ interface, which can play a role in establishing the communication of the dimers.

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