Document Detail


Prediction, refinement, and persistency of transmembrane helix dimers in lipid bilayers using implicit and explicit solvent/lipid representations: microsecond molecular dynamics simulations of ErbB1/B2 and EphA1.
MedLine Citation:
PMID:  23042146     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
All-atom simulations are carried out on ErbB1/B2 and EphA1 transmembrane helix dimers in lipid bilayers starting from their solution/DMPC bicelle NMR structures. Over the course of microsecond trajectories, the structures remain in close proximity to the initial configuration and satisfy the majority of experimental tertiary contact restraints. These results further validate CHARMM protein/lipid force fields and simulation protocols on Anton. Separately, dimer conformations are generated using replica exchange in conjunction with an implicit solvent and lipid representation. The implicit model requires further improvement, and this study investigates whether lengthy all-atom molecular dynamics simulations can alleviate the shortcomings of the initial conditions. The simulations correct many of the deficiencies. For example, excessive helix twisting is eliminated over a period of hundreds of nanoseconds. The helix tilt, crossing angles, and dimer contacts approximate those of the NMR-derived structure, although the detailed contact surface remains off-set for one of two helices in both systems. Hence, even microsecond simulations are not long enough for extensive helix rotations. The alternate structures can be rationalized with reference to interaction motifs and may represent still sought after receptor states that are important in ErbB1/B2 and EphA1 signaling.
Authors:
Liqun Zhang; Alexander J Sodt; Richard M Venable; Richard W Pastor; Matthias Buck
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Publication Detail:
Type:  Journal Article; Research Support, American Recovery and Reinvestment Act; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-05
Journal Detail:
Title:  Proteins     Volume:  81     ISSN:  1097-0134     ISO Abbreviation:  Proteins     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-01-28     Completed Date:  2013-08-02     Revised Date:  2014-03-09    
Medline Journal Info:
Nlm Unique ID:  8700181     Medline TA:  Proteins     Country:  United States    
Other Details:
Languages:  eng     Pagination:  365-76     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Hydrogen Bonding
Lipid Bilayers / chemistry*
Magnetic Resonance Spectroscopy
Molecular Dynamics Simulation*
Molecular Sequence Data
Protein Interaction Mapping
Protein Multimerization*
Protein Structure, Secondary
Receptor, EphA1 / chemistry*
Receptor, erbB-2 / chemistry*
Solvents / chemistry
Static Electricity
Time Factors
Grant Support
ID/Acronym/Agency:
R01 GM073071/GM/NIGMS NIH HHS; R01 GM092851/GM/NIGMS NIH HHS; R01GM073071/GM/NIGMS NIH HHS; R01GM092851/GM/NIGMS NIH HHS; RC2GM0933307/GM/NIGMS NIH HHS; T32DK007470/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Lipid Bilayers; 0/Solvents; EC 2.7.10.1/Receptor, EphA1; EC 2.7.10.1/Receptor, erbB-2
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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