Probing and Manipulating Biomolecules: From Single Molecules to an Ensemble

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Proteins are responsible for the execution of most cellular functions required for life, including amongothers catalysis and molecular recognition within and between cells and their surroundings. Naturalproteins also inspire the engineering of mutants as new catalysts. The proposed research is aimed atenhancing the understanding of protein structure-function relationships by combining single moleculeand ensemble approaches. To achieve this goal, we introduce a synergetic strategy whichinterdigitates theoretical and experimental approaches. We plan to apply: (i) force measurements(DFS) to probe biological molecules in order to alter the extent and even the fate of specific reactions;(ii) synthesis of artificial enzymes and selection of natural enzymes whose efficiency might beenhanced by directed evolution (to be probed by DFS); (iii) parallel studies on protein dynamicscombining single molecule, ensemble average and simulation experiments to explore theinterdependence between their interactions with the cell membrane and their function. The generallong-range goal of the project is to bridge between single molecule and ensemble measurements, gainfurther understanding of structure-energy landscape-function relationship in proteins, and explore thefactors controlling protein diffusion dynamics in cells, which play crucial roles in cellular signalingevents. Our effort will ultimately contribute new insights into specific aspects of the machinery of aliving cell.