<i>In silico</i> investigation of pH-dependence of prolactin and human growth hormone binding to human prolactin receptor.

ABSTRACT: 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'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

SUBMITTER: Wang L 

PROVIDER: S-EPMC3966486 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature