Docking macromolecules with flexible segments

We address a major obstacle to macromolecular docking algorithms by presenting a new method that takes into account the induced conformational adjustment of flexible loops situated at a protein/macromolecule interface. The method, MC2, is based on a multiple copy representation of the loops, coupled...

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Bibliographic Details
Published in:Journal of computational chemistry 2003-11, Vol.24 (15), p.1910-1920
Main Authors: Bastard, Karine, Thureau, Aurélien, Lavery, Richard, Prévost, Chantal
Format: Article
Language:English
Subjects:
Algorithms
Computer Simulation
DNA
DNA - chemistry
docking
flexible loops
internal variables
Ligands
Macromolecular Substances
Models, Biological
molecular modeling
Monte Carlo
Monte Carlo Method
multiple copy
Oligopeptides - chemistry
protein
Protein Binding
Protein Conformation
Protein Folding
Protein Structure, Secondary
Proteins - chemistry
Structure-Activity Relationship
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Summary:We address a major obstacle to macromolecular docking algorithms by presenting a new method that takes into account the induced conformational adjustment of flexible loops situated at a protein/macromolecule interface. The method, MC2, is based on a multiple copy representation of the loops, coupled with a Monte Carlo conformational search of the relative position of the macromolecules and their side chain conformations. The selection of optimal loop conformations takes place during Monte Carlo cycling by the iterative adjustment of the weight of each copy. We describe here the parameterization of the method and trials on a protein‐DNA complex of known 3‐D structure, involving the Drosophila prd paired domain protein and its target oligonucleotide Wenqing, X. et al., Cell 1995, 80, 639. We demonstrate that our algorithm can correctly configure and position this protein, despite its relatively complex interactions with both grooves of DNA. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 1910–1920, 2003
ISSN:0192-8651
1096-987X
DOI:10.1002/jcc.10329