Document Detail

Mapping multiple potential ATP binding sites on the matrix side of the bovine ADP/ATP carrier by the combined use of MD simulation and docking.
MedLine Citation:
PMID:  21989959     Owner:  NLM     Status:  MEDLINE    
The mitochondrial adenosine diphosphate/adenosine triphosphate (ADP/ATP) carrier-AAC-was crystallized in complex with its specific inhibitor carboxyatractyloside (CATR). The protein consists of a six-transmembrane helix bundle that defines the nucleotide translocation pathway, which is closed towards the matrix side due to sharp kinks in the odd-numbered helices. In this paper, we describe the interaction between the matrix side of the AAC transporter and the ATP(4-) molecule using carrier structures obtained through classical molecular dynamics simulation (MD) and a protein-ligand docking procedure. Fifteen structures were extracted from a previously published MD trajectory through clustering analysis, and 50 docking runs were carried out for each carrier conformation, for a total of 750 runs ("MD docking"). The results were compared to those from 750 docking runs performed on the X-ray structure ("X docking"). The docking procedure indicated the presence of a single interaction site in the X-ray structure that was conserved in the structures extracted from the MD trajectory. MD docking showed the presence of a second binding site that was not found in the X docking. The interaction strategy between the AAC transporter and the ATP(4-) molecule was analyzed by investigating the composition and 3D arrangement of the interaction pockets, together with the orientations of the substrate inside them. A relationship between sequence repeats and the ATP(4-) binding sites in the AAC carrier structure is proposed.
Daniele Di Marino; Francesco Oteri; Blasco Morozzo della Rocca; Ilda D'Annessa; Mattia Falconi
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Publication Detail:
Type:  Journal Article     Date:  2011-10-12
Journal Detail:
Title:  Journal of molecular modeling     Volume:  18     ISSN:  0948-5023     ISO Abbreviation:  J Mol Model     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-05-28     Completed Date:  2012-09-20     Revised Date:  2013-03-15    
Medline Journal Info:
Nlm Unique ID:  9806569     Medline TA:  J Mol Model     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  2377-86     Citation Subset:  IM    
Department of Medicine, University of Rome Tor Vergata, Rome, Italy.
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MeSH Terms
Adenosine Triphosphate / chemistry*
Amino Acid Motifs
Binding Sites
Cluster Analysis
Mitochondrial ADP, ATP Translocases / chemistry*
Molecular Dynamics Simulation*
Protein Binding
Protein Structure, Tertiary
Surface Properties
Reg. No./Substance:
56-65-5/Adenosine Triphosphate; 9068-80-8/Mitochondrial ADP, ATP Translocases

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