The principal goal of this project is to develop uses of images derived from electron cryomicroscopy as molecular replacement models for x-ray crystallography. A second goal is to use high-resolution structures of viral proteins and subviral particles, together with cryoEM reconstructions of intact virions, to obtain detailed models for complex viruses. (1) Human papillomavirus 16 (HPV16) small virus-like particles (VLPs) will be used as test objects, to work out the best ways of determining the orientation and position parameters for placing a 3-D image reconstruction in the unit cell of a crystal and to analyze the resulting phase correlations in different resolution shells. We will analyze the effects of CTF corrections, procedures for deriving the reconstructed image, and molecular- replacement algorithms on the phase-determining power of the model. (2) Molecular replacement approaches will be used to solve the phase problem for rotavirus inner capsid particles (ICPs), for the rotavirus outer-shell protein, VP7, and for the retrovirus"""""""" penetration complex"""""""", mu13SIGMA3/3. 93) Crystal structures for components of retrovirus and rotavirus particles will be used, together with EM reconstructions of the intact viruses, to build models for the intact virions.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM062580-02
Application #
6588151
Study Section
Special Emphasis Panel (ZRG1)
Project Start
2002-04-01
Project End
2003-03-31
Budget Start
Budget End
Support Year
2
Fiscal Year
2002
Total Cost
Indirect Cost
Name
Brandeis University
Department
Type
DUNS #
616845814
City
Waltham
State
MA
Country
United States
Zip Code
02454
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