title: Understanding the apparent stator-rotor connections in the rotary ATPase family using coarse-grained computer modeling.
abstract: Advances in structural biology, such as cryo-electron microscopy (cryo-EM) have allowed for a number of sophisticated protein complexes to be characterized. However, often only a static snapshot of a protein complex is visualized despite the fact that conformational change is frequently inherent to biological function, as is the case for molecular motors. Computer simulations provide valuable insights into the different conformations available to a particular system that are not accessible using conventional structural techniques. For larger proteins and protein complexes, where a fully atomistic description would be computationally prohibitive, coarse-grained simulation techniques such as Elastic Network Modeling (ENM) are often employed, whereby each atom or group of atoms is linked by a set of springs whose properties can be customized according to the system of interest. Here we compare ENM with a recently proposed continuum model known as Fluctuating Finite Element Analysis (FFEA), which represents the biomolecule as a viscoelastic solid subject to thermal fluctuations. These two complementary computational techniques are used to answer a critical question in the rotary ATPase family; implicit within these motors is the need for a rotor axle and proton pump to rotate freely of the motor domain and stator structures. However, current single particle cryo-EM reconstructions have shown an apparent connection between the stators and rotor axle or pump region, hindering rotation. Both modeling approaches show a possible role for this connection and how it would significantly constrain the mobility of the rotary ATPase family.
authors.affiliation: School of Physics and Astronomy, University of Leeds, Leeds, United Kingdom.
authors.forename: Robin A
authors.initials: RA
authors.lastname: Richardson
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Papachristos
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Read
authors.forename: Oliver G
authors.initials: OG
authors.lastname: Harlen
authors.forename: Michael
authors.initials: M
authors.lastname: Harrison
authors.forename: Emanuele
authors.initials: E
authors.lastname: Paci
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Muench
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Harris
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D055162:Biocatalysis; D030562:Databases, Protein; D055119:Elastic Modulus; D020342:Finite Element Analysis; D019476:Insect Proteins / Q000737:chemistry* / Q000378:metabolism; D018402:Manduca / Q000201:enzymology; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D025341:Principal Component Analysis; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000737:chemistry* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D016963:Thermus thermophilus / Q000201:enzymology; D025262:Vacuolar Proton-Translocating ATPases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D019476:Insect Proteins; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D025262:Vacuolar Proton-Translocating ATPases; D006180:Proton-Translocating ATPases
keywords: Cryo-EM; ENM; FFEA; PCA; finite element analysis; simulation