Single molecule studies of freely diffusing molecules

2 Single molecule studies of freely diffusing molecules 

This work shows nicely that single molecule measurements on freely diffusing FRET labelled molecules can be used to provide information similar to that which an ensemble experiment would provide, but in addition allows subpopulations in a complex system to be resolved. Improvement in fluorescence probes to reduce photobleaching and conformational flexibility through the use of short, rigid linkers will be necessary to get the best results from this approach. 

3 Studies of protein folding with single molecule sensitivity 

The conformational transformation from the unfolded to the native state of a protein is highly likely to be a heterogeneous process in which many different pathways (i.e. sequences of intermediate conformations) can be taken. 

Understanding the kinetic search across a complex free energy landscape is a major challenge that is ideally addressed by single molecule studies in which the inherent heterogeneity can potentially be unravelled. 

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