Computational Investigations of Biological Nanosystems

1 Overview Understanding life from its molecular foundation to the cellular, organ, and organism levels complements the practice of medicine. In answering the most basic questions about organisms, biomedical researchers import methods and concepts from the physical sciences that encompass novel experiments and mathematical descriptions. Likewise, motivated by biomedically relevant problems and collaborating closely with experimental laboratories, the Theoretical Biophysics Group at the Beckman Institute of the U. of Illinois at Urbana-Champaign exploits advances in physical theory and computing to model organisms across many levels of organization, from molecules to cells to networks. During the past decade, the group has pioneered the modeling of very large biomolec-ular structures that are responsible for key processes in living cells, ranging from metabolism to signaling to cell motion. during the last year of a total funding cycle of nine years. Our group has derived from the Craver funds great benefits and we feel compelled to explain in a section Carver Charitable Trust funds built an important science interface why the support from the Carver Charitable Trust has been important and so extraordinarily successful. Through the Carver support we continued to advance studies in cellular biology, bridging a gap between laboratories where large biomolecular structures are discovered and measured, and computational laboratories where the expertise for very large scale molecular modeling resides. The group has engaged in relevant and demanding collaborations on cellular nanosystems that required large scale modeling and that reached significant results. Our group has pioneered also the use of so-called steered molecular dynamics in which external forces are applied to test reaction pathways and mechanical properties of biopolymers as well as analyze the results. The Carver funded collaborators applied steered molecular dynamics in several new exciting research projects, for example, to understand the expression of genetic information through mechanical control of DNA, the harvesting of sunlight that fuels nearly all life on earth, the transformation of light energy into electrical energy in the form of a proton gradient, useful to the cell, or to the control of the electrical potential of neurons through ion selective membrane channels. All these systems are fundamental and basic to life, yet involve large molecular systems containing ten thousand to hundred thousand atoms that can be handled computationally by very few research groups. Research advances achieved through its unique modeling capabilities are a primary measure of our group's success. Through Carver funds our group collaborates on …