Complementarity of hydrophobic properties in ATP-protein binding: a new criterion to rank docking solutions.

Full Abstract

ATP is an important substrate of numerous biochemical reactions in living cells. Molecular recognition of this ligand by proteins is very important for understanding enzymatic mechanisms. Considerable insight into the problem may be gained via molecular docking simulations. At the same time, standard docking protocols are often insufficient to predict correct conformations for protein-ATP complexes. Thus, in most cases the native-like solutions can be found among the docking poses, but current scoring functions have only limited ability to discriminate them from false positives. To improve the selection of correct docking solutions obtained with the GOLD software, we developed a new ranking criterion specific for ATP-protein binding. The method is based on detailed analysis of the intermolecular interactions in 40 high-resolution 3D structures of ATP-protein complexes (the training set). We found that the most important factors governing this recognition are hydrogen-bonding, stacking between adenine and aromatic protein residues, and hydrophobic contacts between adenine and protein residues. To address the latter, we applied the formalism of 3D molecular hydrophobicity potential. The results obtained were used to construct an ATP-oriented scoring criterion as a linear combination of the terms describing these intermolecular interactions. The criterion was then validated using the test set of 10 additional ATP-protein complexes. As compared with the standard scoring functions, the new ranking criterion significantly improved the selection of correct docking solutions in both sets and allowed considerable enrichment at the top of the list containing docking poses with correct solutions.Copyright 2006 Wiley-Liss, Inc.

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Author information

Author/s: Pyrkov, Timothy V (TV); Kosinsky, Yuri A (YA); Arseniev, Alexander S (AS); Priestle, John P (JP); Jacoby, Edgar (E); Efremov, Roman G (RG);

Affiliation: M.M. Shemyakin & Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya, 16/10, 117997 GSP, Moscow V-437, Russia. pyrkov(-atsign-)nmr.ru

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

Journal: Proteins (Proteins), published in United States. (Language: eng)

Reference: 2007-Feb; vol 66 (issue 2) : pp 388-98

Dates: Created 2006/12/27; Completed 2007/03/06;

PMID: 17094116, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adenine - chemistry; metabolism
Adenosine Triphosphate - metabolism
Algorithms
Animals
Binding Sites
Computer Simulation
Humans
Hydrogen Bonding

Associated Chemicals: Ligands (0) ; Proteins (0) ; Adenosine Triphosphate (56-65-5) ; Adenine (73-24-5)

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