화학공학소재연구정보센터
Journal of Physical Chemistry B, Vol.114, No.35, 11659-11667, 2010
Membrane-Induced Conformational Changes of Kyotorphin Revealed by Molecular Dynamics Simulations
The analgesic dipeptide kyotorphin (L-Tyr-L-Arg) was studied in the two most relevant protonation states at physiological pH, both in water and in a membrane model, using molecular dynamics simulations. Kyotorphin is found to exhibit a remarkable conformational freedom even when strongly interacting with the bilayer. Nevertheless, we observe a strong decrease in the population of the tyrosine's chi(1) torsion angle around 60 degrees that could be correlated with the dipeptide biological function. We employed a linear response approximation methodology to determine the N-terminus pK(a) values of kyotorphin and obtained 7.80 and 7.94 for aqueous and lipidic systems, respectively. Our results also indicate that the interaction of kyotorphin with a biological membrane model is consistent with the "membrane catalyst" hypothesis, and that even after the reduction of conformational freedom due to membrane insertion, this peptide fulfils most of the known constraints present in the opioid-like receptors.