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Characterization of the molten globule state of retinol‐binding protein using a molecular dynamics simulation approach
Author(s) -
Paci Emanuele,
Greene Lesley H.,
Jones Rachel M.,
Smith Lorna J.
Publication year - 2005
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2005.04898.x
Subject(s) - molten globule , molecular dynamics , characterization (materials science) , dynamics (music) , chemistry , state (computer science) , materials science , computer science , protein structure , biochemistry , physics , nanotechnology , computational chemistry , algorithm , acoustics
Retinol‐binding protein transports retinol, and circulates in the plasma as a macromolecular complex with the protein transthyretin. Under acidic conditions retinol‐binding protein undergoes a transition to the molten globule state, and releases the bound retinol ligand. A biased molecular dynamics simulation method has been used to generate models for the ensemble of conformers populated within this molten globule state. Simulation conformers, with a radius of gyration at least 1.1 Å greater than that of the native state, contain on average 37%β‐sheet secondary structure. In these conformers the central regions of the two orthogonal β‐sheets that make up the β‐barrel in the native protein are highly persistent. However, there are sizable fluctuations for residues in the outer regions of the β‐sheets, and large variations in side chain packing even in the protein core. Significant conformational changes are seen in the simulation conformers for residues 85–104 (β‐strands E and F and the E‐F loop). These changes give an opening of the retinol‐binding site. Comparisons with experimental data suggest that the unfolding in this region may provide a mechanism by which the complex of retinol‐binding protein and transthyretin dissociates, and retinol is released at the cell surface.