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Docking macromolecules with flexible segments
Author(s) -
Bastard Karine,
Thureau Aurélien,
Lavery Richard,
Prévost Chantal
Publication year - 2003
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.10329
Subject(s) - macromolecule , docking (animal) , monte carlo method , oligonucleotide , computer science , biological system , dna , algorithm , biophysics , chemistry , crystallography , biology , mathematics , biochemistry , medicine , statistics , nursing
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 m ultiple c opy representation of the loops, coupled with a M onte C arlo 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