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Biopolymer Dynamics

The living cell is an extraordinary organization whose complex functioning is based on a symbiotic relationship between DNA, RNA and proteins. While DNA, RNA and proteins are macromolecules like synthetic polymers; there is a fundamental distinction between them. Several properties of synthetic polymers are essentially independent of molecular chemistry. On the other hand, biopolymers are not only large molecules, but are also devices or machines that carry out very specific operations. Proteins, for instance, act as catalysts for strictly specific reactions, they are responsible for the specific transportation of molecules through membranes, for tangling and untangling knots on DNA, etc. The specific functionality of biopolymers is intimately linked to their structure. The most famous example of structure is the double helix model of DNA. In the case of proteins, there is a complex hierarchy of structures. The simplest is the primary structure, which is the sequence of amino acids in the chain. Secondary structures are patterns that reflect a short-scale order in the spatial positions of the amino acids, typically referred to as alpha-helices and beta-sheets. Finally, there is a long-scale tertiary structure that gives the protein its unique three-dimensional configuration. The central focus of biochemists and biophysicists has been to understand the detailed structures of proteins, and the relationship between structure and function.

A major revolution in the pursuit of these studies has occurred in the last decade due to the development of optical and mechanical probes that are sensitive enough to make measurements on single biomolecules, and consequently give totally new insights into the structure and dynamics of living matter at nanometer scales. The new mechanical tools enable the application of forces that are large enough to induce structural deformation, and consequently probe the three-dimensional structure of the molecules. The parallel development of single molecule detection and single molecule spectroscopy by laser-induced fluorescence has enabled insight into the conformational states and conformational dynamics and activities of single biomolecules. Instead of previous experimental methods that relied on inferences drawn from ensembles of molecules, the new techniques allow one to answer questions about how a protein moves, how it responds to an applied force, how it unfolds, etc. Protein engineering has also played an important role in these investigations by enabling the construction of artificial polyproteins with relatively simple structures that can be used as model systems in these studies.

The centrality of deformation in this new paradigm in molecular biology enables us to draw an analogy with a similar revolution that has occurred in the rheology of polymer solutions, that can be fruitfully exploited to significantly augment the study of biomacromolecules. The central goal of our research is to carry out interdisciplinary research in which the techniques of experimental and theoretical rheology, and advances in protein science are brought to bear, on several physical problems that are firmly grounded in a biological context.

Collaborators

1. T. Sridhar, Monash University
2. E. S. G. Shaqfeh, Stanford University
3. B. Duenweg, Max Planck Institute for Polymer Research
4. P. Sunthar, IIT Mumbai

Funding

1. New Staff Member Research Fund, Monash University
2. Australian Partnership for Advanced Computing, Merit Allocation Scheme
3. Engineering Faculty Grants Scheme, Monash University
4. Monash Research Fund Postdoctoral Fellowships Scheme, Monash University
5. Australian Research Council, Discovery Grants Scheme

Conference Presentations and Publications on this topic

4. T. T. Pham, M. Bajaj, and J. R. Prakash, "Brownian dynamics simulation of polymer collapse in a poor solvent: Influence of implicit hydrodynamic interactions", Soft Matter, 4, 1196 - 1207 (2008).

3. R. Duggal, P. Sunthar, J. R. Prakash, and M. Pasquali, "Multi-scale Simulation of Dilute DNA in a Roll-knife Coating Flow", reprint, 2006.

2. P Sunthar, D. A. Nguyen, R. Dubbelboer, J R. Prakash, and T Sridhar, "Measurement and prediction of the elongational stress growth in a dilute solution of DNA molecules", Macromolecules, 38, 10200-10209 (2005).

1. Sunthar, P. and J. R. Prakash, “Parameter free prediction of DNA conformations in Elongational flow by Successive Fine Graining,” Macromolecules, 38, 617-640 (2005).


4. J. R. Prakash, The Dynamics of Polymer Collapse as a Toy Model for Protein Folding, Biennial Conference of the Australian Association of Von Humboldt Fellows, September 7- 9, 2007, Melbourne, Australia.

3. P Sunthar, D. A. Nguyen, R. Dubbelboer, J R. Prakash, and T Sridhar, Elongational viscosity of dilute solutions of DNA molecules, Society of Rheology 77th Annual Meeting, 16–20 October 2005, Vancouver, Canada.

2. R. Duggal, P. Sunthar, J. R. Prakash, and M. Pasquali, Molecular Conformation of DNA in a Small-scale Coating Flow using a Macro-Micro Approach, AIChE Annual Meeting, 7–12 November 2004, Austin, USA.

1. P. Sunthar and J. R. Prakash, Predictions of the evolution of DNA conformations in an extensional flow, Korean-Australian Rheology Conference, Gyeongju, Korea, 24–26 September 2003.