How is the function of biomolecules in living systems related to their atomic structure?
Professor Doniach's research group uses scattering of synchotron X-rays from electron storage rings at SLAC and at the Argonne National Laboratory to study changes in the conformation of molecules as their solvent environments are changed. The research also involves computer simulations of the dynamics and energetic of the resulting changes.
recent Advances in the biology of DNA have shown that a very large part of the genome in eukaryotes codes for small RNA molecules that appear to be centralto the way the genes (coding for proteins) are put together. Doniach's group is currently studying structural changes that occur when some small functional RNA's turn on and off gene expression (riboswitches) without needing to involve protein transcription factors. Understanding RNA control mechanisms is central to our ability to intervene in biological functions such as generation of biofuels by bacteria or of intervention when cells start to go cancerous.
The Doniach group's bio-simulation work involves new ways to represent changes in molecular structure, in which the entire trajectory for a change of conformation is represented in a large number of CPU's where each time slice of the trajectory is managed by one of the CPU's. In this way, a representationof changes involving thousands of degrees of freedom may be obtained at atomic reslution. This method has recently been applied to look at protein misfolding. Another project involves using a highly simplified normal mode representationto represent large scale conformational changes in molecular motor molecules and DNS polymerase.
The group is also working on ways to improve the methods of computing the statistical mechanics of counter-ion shielding of the very large Coulomb forces endangered by the phosphate backbones of DNA and RNA. Software has been developed that modifies the solving of the Poisson Boltzmann equation to include the effects of finite ion size. Further modifications are being worked in to include effects of ion-on correlations.
Current Area of Focus:
- Membrane Proteins