title: Exploring global distortions of biological macromolecules and assemblies from low-resolution structural information and elastic network theory.
abstract: A theory of elastic normal modes is described for the exploration of global distortions of biological structures and their assemblies based upon low-resolution image data. Structural information at low resolution, e.g. from density maps measured by cryogenic electron microscopy (cryo-EM), is used to construct discrete multi-resolution models for the electron density using the techniques of vector quantization. The elastic normal modes computed based on these discretized low-resolution models are found to compare well with the normal modes obtained at atomic resolution. The quality of the normal modes describing global displacements of the molecular system is found to depend on the resolution of the synthetic EM data and the extent of reductionism in the discretized representation. However, models that reproduce the functional rearrangements of our test set of molecules are achieved for realistic values of experimental resolution. Thus large conformational changes as occur during the functioning of biological macromolecules and assemblies can be elucidated directly from low-resolution structural data through the application of elastic normal mode theory and vector quantization.
authors.affiliation: Department of Molecular Biology (TPC6), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Florence
authors.initials: F
authors.lastname: Tama
authors.forename: Willy
authors.initials: W
authors.lastname: Wriggers
authors.forename: Charles L
authors.initials: CL
authors.lastname: Brooks
mesh_terms: D000263:Adenylate Kinase / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D002645:Chickens; D002950:Citrate (si)-Synthase / Q000737:chemistry* / Q000378:metabolism; D020285:Cryoelectron Microscopy / Q000379:methods; D018360:Crystallography, X-Ray / Q000379:methods; D004548:Elasticity; D004926:Escherichia coli; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D046911:Macromolecular Substances; D008958:Models, Molecular; D033902:Periplasmic Binding Proteins; D011487:Protein Conformation; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D002352:Carrier Proteins; D029968:Escherichia coli Proteins; D046911:Macromolecular Substances; C461619:MalE protein, E coli; D033902:Periplasmic Binding Proteins; D002950:Citrate (si)-Synthase; D000263:Adenylate Kinase