Abstract:
The n-terminal domain (163 residues) of human thrombopoietin (htpo) is highly conserved and responsible for the receptor-binding. The crystal structure of free htpo is not yet available, but the crystal structure of its receptor-binding domain (htpo163) is available in complex with the tn1-fab antibody. According to a thermodynamic study of htpo163 binding to tn1-fab ab, the δh value for binding becomes more negative with an increase in temperature from 283 k to 303 k. The objective of our study is to understand how the free htpo163 behaves dynamically and to study the effect of temperature on the association of htpo163 to tn1-fab antibody through molecular dynamics simulations. We studied the ag-ab interactions at two different temperatures 298 k and 303 k. The discontinuous epitope region (residues 98–115) of free htpo163 displays a conformational switch and it gets stabilized upon binding to the ab at 303 k. Based on our results, it may be surmised that the epitope region 98–115 is behaving like a disordered epitope. The disordered epitopes are known to be more efficient in binding with the antibody. We also find that, there is an increase in number of hydrogen-bonding interactions and hydrophobic contacts with an increase in the temperature from 298 k to 303 k. Thus, this observation explains a possible reason behind the more negative value of δh at the higher temperature 303 k as compared to 298 k. © 2021 elsevier inc.