Prediction of structures of zinc-binding proteins through explicit modeling of metal coordination geometry

TitlePrediction of structures of zinc-binding proteins through explicit modeling of metal coordination geometry
Publication TypeJournal Article
Year of Publication2010
AuthorsWang, C., Vernon R., Lange O., Tyka M., & Baker D.
JournalProtein science
Volume19
Issue3
Pagination494-506
Date Published2010 Mar
ISSN1469-896X
KeywordsCarrier Proteins, Computer Simulation, Models, Molecular, Primary Publication, Protein Conformation, Protein Folding, Sequence Analysis, Protein, Software, Zinc
Abstract

Metal ions play an essential role in stabilizing protein structures and contributing to protein function. Ions such as zinc have well-defined coordination geometries, but it has not been easy to take advantage of this knowledge in protein structure prediction efforts. Here, we present a computational method to predict structures of zinc-binding proteins given knowledge of the positions of zinc-coordinating residues in the amino acid sequence. The method takes advantage of the "atom-tree" representation of molecular systems and modular architecture of the Rosetta3 software suite to incorporate explicit metal ion coordination geometry into previously developed de novo prediction and loop modeling protocols. Zinc cofactors are tethered to their interacting residues based on coordination geometries observed in natural zinc-binding proteins. The incorporation of explicit zinc atoms and their coordination geometry in both de novo structure prediction and loop modeling significantly improves sampling near the native conformation. The method can be readily extended to predict protein structures bound to other metal and/or small chemical cofactors with well-defined coordination or ligation geometry.

Alternate JournalProtein Sci.
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