title: Computational reconstruction of multidomain proteins using atomic force microscopy data.
abstract: Classical structural biology techniques face a great challenge to determine the structure at the atomic level of large and flexible macromolecules. We present a novel methodology that combines high-resolution AFM topographic images with atomic coordinates of proteins to assemble very large macromolecules or particles. Our method uses a two-step protocol: atomic coordinates of individual domains are docked beneath the molecular surface of the large macromolecule, and then each domain is assembled using a combinatorial search. The protocol was validated on three test cases: a simulated system of antibody structures; and two experimentally based test cases: Tobacco mosaic virus, a rod-shaped virus; and Aquaporin Z, a bacterial membrane protein. We have shown that AFM-intermediate resolution topography and partial surface data are useful constraints for building macromolecular assemblies. The protocol is applicable to multicomponent structures connected in the polypeptide chain or as disjoint molecules. The approach effectively increases the resolution of AFM beyond topographical information down to atomic-detail structures.
authors.affiliation: CEA, iBEB, Department of Biochemistry and Nuclear Toxicology, F-30207 Bagnols sur Cèze, France.
authors.forename: Minh-Hieu
authors.initials: MH
authors.lastname: Trinh
authors.forename: Michael
authors.initials: M
authors.lastname: Odorico
authors.forename: Michael E
authors.initials: ME
authors.lastname: Pique
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Teulon
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Roberts
authors.forename: Lynn F
authors.initials: LF
authors.lastname: Ten Eyck
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Getzoff
authors.forename: Pierre
authors.initials: P
authors.lastname: Parot
authors.forename: Shu-Wen W
authors.initials: SW
authors.lastname: Chen
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Pellequer
mesh_terms: D020346:Aquaporins / Q000737:chemistry; D019295:Computational Biology / Q000379:methods*; D029968:Escherichia coli Proteins / Q000737:chemistry; D018625:Microscopy, Atomic Force / Q000379:methods*; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D014027:Tobacco Mosaic Virus / Q000737:chemistry
chemical_list: D020346:Aquaporins; D029968:Escherichia coli Proteins; D011506:Proteins; C106425:aqpZ protein, E coli