@Article{CiCP-13-1,
author = {},
title = {In Silico Investigation of pH-Dependence of Prolactin and Human Growth Hormone Binding to Human Prolactin Receptor},
journal = {Communications in Computational Physics},
year = {2013},
volume = {13},
number = {1},
pages = {207--222},
abstract = {<p style="text-align: justify;">Experimental data shows that the binding of human prolactin (hPRL) to human prolactin receptor (hPRLr-ECD) is strongly pH-dependent, while the binding of
the same receptor to human growth hormone (hGH) is pH-independent. Here we
carry in silico analysis of the molecular effects causing such a difference and reveal the
role of individual amino acids. It is shown that the computational modeling correctly
predicts experimentally determined pKa&#39;s of histidine residues in an unbound state
in the majority of the cases and the pH-dependence of the binding free energy. Structural analysis carried in conjunction with calculated pH-dependence of the binding
revealed that the main reason for pH-dependence of the binding of hPRL-hPRLr-ECD
is a number of salt-bridges across the interface of the complex, while no salt-bridges are
formed in the hGH-hPRlr-ECD. Specifically, most of the salt-bridges involve histidine
residues and this is the reason for the pH-dependence across a physiological range of
pH. The analysis not only revealed the molecular mechanism of the pH-dependence
of the hPRL-hPRLr-ECD, but also provided critical insight into the underlying physic-chemical mechanism.</p>},
issn = {1991-7120},
doi = {https://doi.org/10.4208/cicp.170911.131011s},
url = {https://global-sci.com/article/80616/in-silico-investigation-of-ph-dependence-of-prolactin-and-human-growth-hormone-binding-to-human-prolactin-receptor}
}