Ab initio modeling of the herpesvirus VP26 core domain assessed by CryoEM density

TitleAb initio modeling of the herpesvirus VP26 core domain assessed by CryoEM density
Publication TypeJournal Article
Year of Publication2006
AuthorsBaker, M. L., Jiang W., Wedemeyer W. J., Rixon F. J., Baker D., & Chiu W.
JournalPLoS computational biology
Volume2
Issue10
Paginatione146
Date Published2006 Oct 27
ISSN1553-7358
KeywordsAbsorptiometry, Photon, Amino Acid Sequence, Capsid Proteins, Collaborative Publication, Computer Simulation, Cryoelectron Microscopy, Crystallography, Models, Chemical, Models, Molecular, Molecular Sequence Data, Protein Conformation, Protein Structure, Tertiary
Abstract

Efforts in structural biology have targeted the systematic determination of all protein structures through experimental determination or modeling. In recent years, 3-D electron cryomicroscopy (cryoEM) has assumed an increasingly important role in determining the structures of these large macromolecular assemblies to intermediate resolutions (6-10 A). While these structures provide a snapshot of the assembly and its components in well-defined functional states, the resolution limits the ability to build accurate structural models. In contrast, sequence-based modeling techniques are capable of producing relatively robust structural models for isolated proteins or domains. In this work, we developed and applied a hybrid modeling approach, utilizing cryoEM density and ab initio modeling to produce a structural model for the core domain of a herpesvirus structural protein, VP26. Specifically, this method, first tested on simulated data, utilizes the cryoEM density map as a geometrical constraint in identifying the most native-like models from a gallery of models generated by ab initio modeling. The resulting model for the core domain of VP26, based on the 8.5-A resolution herpes simplex virus type 1 (HSV-1) capsid cryoEM structure and mutational data, exhibited a novel fold. Additionally, the core domain of VP26 appeared to have a complementary interface to the known upper-domain structure of VP5, its cognate binding partner. While this new model provides for a better understanding of the assembly and interactions of VP26 in HSV-1, the approach itself may have broader applications in modeling the components of large macromolecular assemblies.

Alternate JournalPLoS Comput. Biol.
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