Our study will quantify the compressive properties of the structural domains of various proteins. We will perform computer simulations (and some analytical work) to gain insight into how nature supports the generation of mechanical force. Specifically, our work will consist of three parts: molecular dynamics simulations will be used to investigate the structural domains of a single subunit of the GroEL chaperone, the mechanical response of the structural domains of the subunits of various molecular machines will be investigated via normal mode and strain tensor analysis, and a novel technique involving Brownian dynamics be used to study force propagation through structural domains. In the distant future we hope that the results of our investigations will be employed by bioengineers to design force-generating machines to prevent and fight diseases such as Alzheimer's, Parkinson's, and countless others. Our proposal requires that we implement some of the latest technologies in the field of molecular simulation and the development of some novel techniques. Finally, our results will not only be comparable with experiment, but they will also provide a conceptual framework for understanding the workings of a class of nanomachines. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM077940-02
Application #
7235378
Study Section
Special Emphasis Panel (ZRG1-F04B-P (20))
Program Officer
Flicker, Paula F
Project Start
2006-06-01
Project End
2008-11-30
Budget Start
2007-06-01
Budget End
2008-05-31
Support Year
2
Fiscal Year
2007
Total Cost
$48,796
Indirect Cost
Name
University of Maryland College Park
Department
Other Basic Sciences
Type
Other Domestic Higher Education
DUNS #
790934285
City
College Park
State
MD
Country
United States
Zip Code
20742
Pincus, David L; Thirumalai, D (2009) Crowding effects on the mechanical stability and unfolding pathways of ubiquitin. J Phys Chem B 113:359-68
Pincus, David L; Hyeon, Changbong; Thirumalai, D (2008) Effects of trimethylamine N-oxide (TMAO) and crowding agents on the stability of RNA hairpins. J Am Chem Soc 130:7364-72