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Molecular basis of the structural stability of hemochromatosis factor E : A combined molecular dynamic simulation and GdmCl‐induced denaturation study
Author(s) -
Khan Parvez,
Parkash Amresh,
Islam Asimul,
Ahmad Faizan,
Hassan Md. Imtaiyaz
Publication year - 2016
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.22760
Subject(s) - chemistry , denaturation (fissile materials) , guanidinium chloride , molecular dynamics , hereditary hemochromatosis , circular dichroism , biophysics , crystallography , biochemistry , computational chemistry , nuclear chemistry , hemochromatosis , enzyme , medicine , biology , gastroenterology
Hemochromatosis factor E (HFE) is a member of class I MHC family and plays a significant role in the iron homeostasis. Denaturation of HFE induced by guanidinium chloride (GdmCl) was measured by monitoring changes in [ θ ] 222 (mean residue ellipticity at 222 nm), intrinsic fluorescence emission intensity at 346 nm (F 346 ) and the difference absorption coefficient at 287 nm (Δ ε 287 ) at pH 8.0 and 25°C. Coincidence of denaturation curves of these optical properties suggests that GdmCl‐induced denaturation (native (N) state ↔ denatured (D) state) is a two‐state process. The GdmCl‐induced denaturation was found reversible in the entire concentration range of the denaturant. All denaturation curves were analyzed forΔ G D 0 , Gibbs free energy change associated with the denaturation equilibrium (N state ↔ D state) in the absence of GdmCl, which is a measure of HFE stability. We further performed molecular dynamics simulation for 40 ns to see the effect of GdmCl on the structural stability of HFE. A well defined correlation was established between in vitro and in silico studies. © 2015 Wiley Periodicals, Inc. Biopolymers 105: 133–142, 2016.