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Understanding the apparent stator‐rotor connections in the rotary ATP ase family using coarse‐grained computer modeling
Author(s) -
Richardson Robin A.,
Papachristos Konstantinos,
Read Daniel J.,
Harlen Oliver G.,
Harrison Michael,
Paci Emanuele,
Muench Stephen P.,
Harris Sarah A.
Publication year - 2014
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.24680
Subject(s) - stator , molecular motor , molecular machine , rotor (electric) , axle , biological system , aaa proteins , computer science , physics , nanotechnology , atpase , materials science , mechanical engineering , engineering , biology , nuclear magnetic resonance , enzyme
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. Proteins 2014; 82:3298–3311. © 2014 The Authors. Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.