title: Origin of mechanical strength of bovine carbonic anhydrase studied by molecular dynamics simulation.
abstract: The forced unfolding process of bovine carbonic anhydrase II (BCA II) was examined at the atomic level by the molecular dynamics (MD) simulation. By force spectroscopy, experimentally obtained force-extension curves (F-E curves) showed a prominent force peak after 50 nm extension. F-E curves obtained from our simulation had three force peaks appearing after extensions of 10-17 nm, 40 nm, and 53 nm, each signifying a brittle fracture of a specific local structure. Upon undergoing the final fracture at 53 nm of extension, the entire molecule became a single flexible chain and was further extended to its full theoretical length, almost as a random coil. This feature of the 53-nm peak strongly suggested its close correspondence to the experimentally observed force peak at approximately 60-nm extension. The 53-nm peak in the molecular dynamics simulation corresponded to the unfolding process of the beta-sheeted core that includes zinc-coordinating histidine residues. These results suggest that the structural change occurring at 50-60 nm in atomic force microscopy experiments corresponded to the destruction of the zinc coordination site.
authors.affiliation: Laboratory of Biodynamics, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Tokyo, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Ohta
authors.forename: Mohammad Taufiq
authors.initials: MT
authors.lastname: Alam
authors.forename: Hideo
authors.initials: H
authors.lastname: Arakawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ikai
mesh_terms: D000818:Animals; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000648:ultrastructure*; D002417:Cattle; D003198:Computer Simulation; D004548:Elasticity; D008846:Micromanipulation / Q000379:methods*; D018625:Microscopy, Atomic Force / Q000379:methods*; D008956:Models, Chemical; D008958:Models, Molecular; D011487:Protein Conformation; D011489:Protein Denaturation; D013314:Stress, Mechanical; D013329:Structure-Activity Relationship; D013718:Tensile Strength
chemical_list: D002256:Carbonic Anhydrases