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. ? ? ?
| 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 |
