| Self-assembly, design and properties of biological nanoparticles | ||
|
Self-assembly processes are ubiquitous in nature and direct the
formation of complex biological systems. Natural materials can
self-assemble at ambient conditions and response in a specific
manner to internal and external stimuli. Nucleic acids (NA), such as
RNA and DNA molecules, are especially appealing candidates for
assembly of natural and synthetic materials due to their versatility
in function and structure, generation of low immune response, and
molecular recognition properties of base pairing. Using these
properties DNA and RNA molecules were engineered into novel
nanostructures to make up effective 2D and 3D nanoparticles,
nanotubes, drug delivery capsules, and scaffolds for the assembly of
molecules or electronic components. Yet there are several challenges
that must be addressed for the success of these applications
including improved efficiency of formation by minimizing errors
during self-assembly, improved responsiveness of the final
structure, control over the hybridization dynamics and final
structure of NA nanostructures and nanomaterials. Our goal is to develop a fundamental understanding of the processes driving the self-assembly of nucleic acids that will ultimately lead to the development of NAs materials as a responsive drug delivery tool and novel bioscaffolds. Moreover, further investigation of molecular self-assembly mechanisms will allow us to build a more complete picture of the structures and functions of natural NAs. Our long term research goal is to learn from Nature and explain how to control biomaterials assembly and disassembly at a specific location and in response to a specific stimuli. We will use molecular modeling techniques to provide a complete microscopic description of the structure and dynamics of NAs under different environmental conditions, from detailed information on atom-to-atom interactions with ions, small molecules, and proteins to global functionally important motions and conformational changes which control the processes of self-assembly. |
 |
|
|
Functionalization of nanoparticles |
||
The main objective here is to attain fundamental
understanding of the role of nanoparticle functional groups in
molecular recognition properties and directed and programmable
self-assembly. Specifically, the following functional groups are
being explored:
|
|
|
|
RNA structure-function relationship and tertiary structure prediction of RNA |
||
| Knowledge of RNA
tertiary structure and dynamics is crucial to understanding its
function and mechanism in the cell.
We have developed a molecular modeling approach for the first-order RNA tertiary structure prediction and successfully applied it to predict structures of the wild-type telomerase RNA pseudoknot domain and other viral RNAs. For example, we predicted a wild-type telomerase pseudoknot structure and examined its folding and formation of various tertiary interactions. The effect of genetic DKC mutations (dyskeratosis congenita) of the 3D pseudoknot structure revealed significant change in stability and disruption of hydrogen bonding in the pseudoknot P3 region.
|
|
|
