title: Symmetry-restrained flexible fitting for symmetric EM maps.
abstract: Many large biological macromolecules have inherent structural symmetry, being composed of a few distinct subunits, repeated in a symmetric array. These complexes are often not amenable to traditional high-resolution structural determination methods, but can be imaged in functionally relevant states using cryo-electron microscopy (cryo-EM). A number of methods for fitting atomic-scale structures into cryo-EM maps have been developed, including the molecular dynamics flexible fitting (MDFF) method. However, quality and resolution of the cryo-EM map are the major determinants of a method's success. In order to incorporate knowledge of structural symmetry into the fitting procedure, we developed the symmetry-restrained MDFF method. The new method adds to the cryo-EM map-derived potential further restraints on the allowed conformations of a complex during fitting, thereby improving the quality of the resultant structure. The benefit of using symmetry-based restraints during fitting, particularly for medium to low-resolution data, is demonstrated for three different systems.
authors: Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors: Kwok-Yan
authors: KY
authors: Chan
authors: James
authors: J
authors: Gumbart
authors: Ryan
authors: R
authors: McGreevy
authors: Jean M
authors: JM
authors: Watermeyer
authors: B Trevor
authors: BT
authors: Sewell
authors: Klaus
authors: K
authors: Schulten
mesh_terms: D000465:Algorithms; D000619:Aminohydrolases / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry; D018835:Chaperonin 10 / Q000737:chemistry; D018834:Chaperonin 60 / Q000737:chemistry; D020285:Cryoelectron Microscopy / Q000379:methods*; D003627:Data Interpretation, Statistical; D056385:Group II Chaperonins / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation
chemical_list: D001426:Bacterial Proteins; D018835:Chaperonin 10; D018834:Chaperonin 60; D000619:Aminohydrolases; C021867:nitrilase; D056385:Group II Chaperonins