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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.

TitleMapping multiple potential ATP binding sites on the matrix side of the bovine ADP/ATP carrier by the combined use of MD simulation and docking.
Publication TypeJournal Article
Year of Publication2012
AuthorsDi Marino, D, Oteri, F, Rocca, BMorozzo de, D'Annessa, I, Falconi, M
JournalJ Mol Model
Volume18
Issue6
Pagination2377-86
Date Published2012 Jun
ISSN0948-5023
KeywordsAdenosine Triphosphate, Amino Acid Motifs, Animals, Binding Sites, Cattle, Cluster Analysis, Mitochondrial ADP, ATP Translocases, Molecular Dynamics Simulation, Protein Binding, Protein Structure, Tertiary, Surface Properties, Thermodynamics
Abstract

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.

DOI10.1007/s00894-011-1255-5
Alternate JournalJ Mol Model
PubMed ID21989959

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