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Determining macromolecular assembly structures by molecular docking and fitting into an electron density map
Author(s) -
Lasker Keren,
Sali Andrej,
Wolfson Haim J.
Publication year - 2010
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.22845
Subject(s) - docking (animal) , molecular model , searching the conformational space for docking , macromolecule , biological system , molecular dynamics , computer science , chemistry , computational biology , computational chemistry , protein structure , biology , stereochemistry , biochemistry , nursing , medicine
Structural models of macromolecular assemblies are instrumental for gaining a mechanistic understanding of cellular processes. Determining these structures is a major challenge for experimental techniques, such as X‐ray crystallography, NMR spectroscopy and electron microscopy (EM). Thus, computational modeling techniques, including molecular docking, are required. The development of most molecular docking methods has so far been focused on modeling of binary complexes. We have recently introduced the MultiFit method for modeling the structure of a multisubunit complex by simultaneously optimizing the fit of the model into an EM density map of the entire complex and the shape complementarity between interacting subunits. Here, we report algorithmic advances of the MultiFit method that result in an efficient and accurate assembly of the input subunits into their density map. The successful predictions and the increasing number of complexes being characterized by EM suggests that the CAPRI challenge could be extended to include docking‐based modeling of macromolecular assemblies guided by EM. Proteins 2010. © 2010 Wiley‐Liss, Inc.