Document Detail

Simulation studies of the mechanism of membrane transporters.
MedLine Citation:
PMID:  23034756     Owner:  NLM     Status:  MEDLINE    
Membrane transporters facilitate active transport of their specific substrates, often against their electrochemical gradients across the membrane, through coupling the process to various sources of cellular energy, for example, ATP binding and hydrolysis in primary transporters, and pre-established electrochemical gradient of molecular species other than the substrate in the case of secondary transporters. In order to provide efficient energy-coupling mechanisms, membrane transporters have evolved into molecular machines in which stepwise binding, translocation, and transformation of various molecular species are closely coupled to protein conformational changes that take the transporter from one functional state to another during the transport cycle. Furthermore, in order to prevent the formation of leaky states and to be able to pump the substrate against its electrochemical gradient, all membrane transporters use the widely-accepted "alternating access mechanism," which ensures that the substrate is only accessible from one side of the membrane at a given time, but relies on complex and usually global protein conformational changes that differ for each family of membrane transporters. Describing the protein conformational changes of different natures and magnitudes is therefore at the heart of mechanistic studies of membrane transporters. Here, using a number of membrane transporters from diverse families, we present common protocols used in setting up and performing molecular dynamics simulations of membrane transporters and in analyzing the results, in order to characterize relevant motions of the system. The emphasis will be on highlighting how optimal design of molecular dynamics simulations combined with mechanistically oriented analysis can shed light onto key functionally relevant protein conformational changes in this family of membrane proteins.
Giray Enkavi; Jing Li; Paween Mahinthichaichan; Po-Chao Wen; Zhijian Huang; Saher A Shaikh; Emad Tajkhorshid
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Methods in molecular biology (Clifton, N.J.)     Volume:  924     ISSN:  1940-6029     ISO Abbreviation:  Methods Mol. Biol.     Publication Date:  2013  
Date Detail:
Created Date:  2012-10-04     Completed Date:  2013-02-20     Revised Date:  2013-04-11    
Medline Journal Info:
Nlm Unique ID:  9214969     Medline TA:  Methods Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  361-405     Citation Subset:  IM    
Department of Biochemistry, Center for Biophysics and Computational Biology, College of Medicine, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
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MeSH Terms
Adenosine Triphosphate / metabolism
Biological Transport
Membrane Transport Proteins / chemistry*,  metabolism*
Molecular Dynamics Simulation*
Neurotransmitter Agents / metabolism
Protein Conformation
Sodium / metabolism
Grant Support
Reg. No./Substance:
0/Membrane Transport Proteins; 0/Neurotransmitter Agents; 56-65-5/Adenosine Triphosphate; 7440-23-5/Sodium

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