Membrane protein structure in lipido: computational developments. This application is in response to Program Announcement PA-10-228 for Structural Biology of Membrane Proteins. The overall goal of the project is to develop new computational methods for NMR structural analysis of integral membrane proteins within their functional environment of the phospholipid bilayer membrane. These protein/lipid macromolecular complexes can be characterized using NMR spectroscopy. The experimental aspects of biomolecular NMR (sample preparation, instrumentation, pulse sequences) have reached an advanced level;however, computational methods are lagging behind. We propose to close this technology gap with three specific aims designed to facilitate structure determination and increase structural quality. To facilitate structure determination and broaden the impact of our work, our methods will be integrated with widely used programs for NMR structure refinement by restrained molecular dynamics and de novo protein structure prediction. To maximize the structural quality and information content, our methods will be tailored for the membrane-specific structural restraints provided by the experimental data.

Public Health Relevance

Membrane proteins play fundamental roles in human health and are the targets of most human therapeutic drugs. Facilitating their structure determination, as proposed in this project, is critical for advancing medical and pharmaceutical research.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
1R01GM110658-01
Application #
8686588
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Chin, Jean
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Sanford-Burnham Medical Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037