Computational Study of the Dimerization of the Parathyroid Hormone

甲状旁腺激素二聚化的计算研究

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Abstract

We present computer simulations of the dimerization process of three different parathyroid horomone (PTH) segments, PTH(34), PTH(42), and PTH(84). A thermodynamic analysis reveals that the aggregation is driven and determined by the N-terminal segment PTH(34) alone. Our simulation model is a coarse-grained one but we can translate the temperature scale of our simulation to physical units by comparison of chain size with experimental data. From this, we can identify that the dimerization and concomitant chain folding occurs only slightly above physiological temperature conditions. The noncooperativity of the dimerization process and its vicinity to physiological conditions give rise to the reversibility of the aggregation of PTH and the functional use of PTH fibrils as storage devices.

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