Document Detail


The gramicidin channel ion permeation free-energy profile: direct and indirect effects of CHARMM force field improvements.
MedLine Citation:
PMID:  20084184     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A revised CHARMM force field for tryptophan residues is studied as well as a new grid-based correction algorithm, called CMAP, using molecular dynamics simulations of gramicidin A (1JNO) embedded in a lipid bilayer (DMPC) with 1 mol/kg NaCl or KCl saline solution. The conformational stability of the interfacial side chains is studied, which shows good stability on the 10 ns time scale. The revised force field for the tryptophan side chain produces, in the decomposition, a Na(+) PMF(Trp) profile that is consonant with the prediction from the experimental results, analyzed with rate theory by Durrant et al. (2006), but in stark contrast to the prediction of the original CHARMM force field, version 22. However, the effect is diluted in the PMF profile due to indirect effects mediated by other components of the system (polypeptide, lipid molecules, ions, and water molecules). CMAP corrections to the L-amino acids help reduce the excessive translocation barrier. Decomposition demonstrates that this effect is due to effects on the K(+) PMF(H(2)O) profile rather than on the K(+) PMF(gA) profile. The results have been confirmed to be robust using an alternative umbrella-potential method. Further force field balancing efforts (direct and indirect) are required for future studies to evaluate whether these effects give rise to predictions that are consistent with those observables extracted from real experiments.
Authors:
Morad Mustafa; David D Busath
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Interdisciplinary sciences, computational life sciences     Volume:  1     ISSN:  1913-2751     ISO Abbreviation:  Interdiscip Sci     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2010-07-28     Completed Date:  2010-09-13     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  101515919     Medline TA:  Interdiscip Sci     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  113-27     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Algorithms
Amino Acids / chemistry
Biophysics / methods
Cations
Computer Simulation
Gramicidin / chemistry*
Ions*
Models, Molecular
Models, Statistical
Molecular Conformation
Sodium / chemistry
Software
Stress, Mechanical
Tryptophan / chemistry
Grant Support
ID/Acronym/Agency:
AI23007/AI/NIAID NIH HHS; R01 AI023007/AI/NIAID NIH HHS; R01 AI023007-22/AI/NIAID NIH HHS; R01 AI073891/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Cations; 0/Ions; 1405-97-6/Gramicidin; 8DUH1N11BX/Tryptophan; 9NEZ333N27/Sodium
Comments/Corrections

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