title: Conformational flexibility of pyruvate dehydrogenase complexes: a computational analysis by quantized elastic deformational model.
abstract: Pyruvate dehydrogenase complex (PDC) is one of the largest multienzyme complexes known and consists of a dodecahedral E2 core to which other components are attached. We report the results of applying a new computational method, quantized elastic deformational model, to simulating the conformational fluctuations of the truncated E2 core, using low-resolution electron cryomicroscopy density maps. The motional features are well reproduced; especially, the symmetric breathing mode revealed in simulation is nearly identical with what was observed experimentally. Structural details of the motions of the trimeric building blocks, which are critical to facilitating the global expansion and contraction of the complex, were revealed. Using the low-resolution maps from electron cryomicroscopy reconstructions, the simulations showed a picture of the motional mechanism of the PDC core, which is an example without precedent of thermally activated global dynamics. Moreover, the current results support an earlier suggestion that, at low resolution and without the use of amino acid sequence and atomic coordinates, it is possible for computer simulations to provide an accurate description of protein dynamics.
authors.affiliation: Graduate Program of Structural and Computational Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Kong
authors.forename: Dengming
authors.initials: D
authors.lastname: Ming
authors.forename: Yinghao
authors.initials: Y
authors.lastname: Wu
authors.forename: James K
authors.initials: JK
authors.lastname: Stoops
authors.forename: Z Hong
authors.initials: ZH
authors.lastname: Zhou
authors.forename: Jianpeng
authors.initials: J
authors.lastname: Ma
mesh_terms: D000123:Acetyltransferases / Q000737:chemistry / Q000378:metabolism; D003198:Computer Simulation; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D051047:Dihydrolipoyllysine-Residue Acetyltransferase; D001411:Geobacillus stearothermophilus / Q000201:enzymology; D046911:Macromolecular Substances; D008958:Models, Molecular; D011487:Protein Conformation; D011768:Pyruvate Dehydrogenase Complex / Q000737:chemistry* / Q000378:metabolism; D011789:Quantum Theory; D012441:Saccharomyces cerevisiae / Q000201:enzymology
chemical_list: D046911:Macromolecular Substances; D011768:Pyruvate Dehydrogenase Complex; D000123:Acetyltransferases; D051047:Dihydrolipoyllysine-Residue Acetyltransferase