An interaction-motif-based scoring function for protein-ligand docking

A good scoring function is essential for molecular docking computations. In conventional scoring functions, energy terms modeling pairwise interactions are cumulatively summed, and the best docking solution is selected. Here, we propose to transform protein-ligand interactions into three-dimensional...

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Bibliographic Details
Published in:BMC bioinformatics 2010-06, Vol.11 (1), p.298-298, Article 298
Main Authors: Xie, Zhong-Ru, Hwang, Ming-Jing
Format: Article
Language:English
Subjects:
Binding Sites
Bioinformatics
Computational biology
Computational Biology - methods
Computer programs
Conformation
Databases, Protein
Energy
Enumeration
Ligands
Mathematical models
Protein Conformation
Protein-protein interactions
Proteins
Proteins - chemistry
Proteins - metabolism
Statistical analysis
Studies
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Summary:A good scoring function is essential for molecular docking computations. In conventional scoring functions, energy terms modeling pairwise interactions are cumulatively summed, and the best docking solution is selected. Here, we propose to transform protein-ligand interactions into three-dimensional geometric networks, from which recurring network substructures, or network motifs, are selected and used to provide probability-ranked interaction templates with which to score docking solutions. A novel scoring function for protein-ligand docking, MotifScore, was developed. It is non-energy-based, and docking is, instead, scored by counting the occurrences of motifs of protein-ligand interaction networks constructed using structures of protein-ligand complexes. MotifScore has been tested on a benchmark set established by others to assess its ability to identify near-native complex conformations among a set of decoys. In this benchmark test, 84% of the highest-scored docking conformations had root-mean-square deviations (rmsds) below 2.0 A from the native conformation, which is comparable with the best of several energy-based docking scoring functions. Many of the top motifs, which comprise a multitude of chemical groups that interact simultaneously and make a highly significant contribution to MotifScore, capture recurrent interacting patterns beyond pairwise interactions. While providing quite good docking scores, MotifScore is quite different from conventional energy-based functions. MotifScore thus represents a new, network-based approach for exploring problems associated with molecular docking.
ISSN:1471-2105
1471-2105
DOI:10.1186/1471-2105-11-298