title: Forced Unfolding Mechanism of Bacteriorhodopsin as Revealed by Coarse-Grained Molecular Dynamics.
abstract: Developments in atomic force microscopy have opened up a new path toward single-molecular phenomena; in particular, during the process of pulling a membrane protein out of a lipid bilayer. However, the characteristic features of the force-distance (F-D) curve of a bacteriorhodopsin in purple membrane, for instance, have not yet been fully elucidated in terms of physicochemical principles. To address the issue, we performed a computer simulation of bacteriorhodopsin with, to our knowledge, a novel coarse-grained (C-G) model. Peptide planes are represented as rigid spheres, while the surrounding environment consisting of water solvents and lipid bilayers is represented as an implicit continuum. Force-field parameters were determined on the basis of auxiliary simulations and experimental values of transfer free energy of each amino acid from water to membrane. According to Popot's two-stage model, we separated molecular interactions involving membrane proteins into two parts: I) affinity of each amino acid to the membrane and intrahelical hydrogen bonding between main chain peptide bonds; and II) interhelix interactions. Then, only part I was incorporated into the C-G model because we assumed that the part plays a dominant role in the forced unfolding process. As a result, the C-G simulation has successfully reproduced the key features, including peak positions, of the experimental F-D curves in the literature, indicating that the peak positions are essentially determined by the residue-lipid and intrahelix interactions. Furthermore, we investigated the relationships between the energy barrier formation on the forced unfolding pathways and the force peaks of the F-D curves.
authors.affiliation: Graduate School of Science, Nagoya University, Nagoya, Aichi, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Graduate School of Science, Nagoya University, Nagoya, Aichi, Japan. Electronic address: yamato@nagoya-u.jp.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Yamato
authors.affiliation: Toyota Physical & Chemical Research Institute, Nagakute, Aichi, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Mitaku
mesh_terms: D001436:Bacteriorhodopsins / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D058767:Protein Unfolding; D013816:Thermodynamics; D014783:Viscosity
chemical_list: D001436:Bacteriorhodopsins