Atomic force microscopy single-molecule studies

Experimental techniques based on the application of mechanical forces to single molecules in small assemblies have been applied to study the binding properties of biomolecules and their response to external mechanical manipulations. Among such techniques are atomic force microscopy (AFM), optical tweezers, biomembrane force probe, and surface force apparatus experiments (Binning et al., 1986 Block and Svoboda, 1994 Evans et ah, 1995 Israelachvili, 1992). These techniques have inspired us and others (see also the chapters by Eichinger et al. and by Hermans et al. in this volume) to adopt a similar approach for the study of biomolecules by means of computer simulations. 

As an example for an efficient yet quite accurate approximation, in the first part of our contribution we describe a combination of a structure adapted multipole method with a multiple time step scheme (FAMUSAMM — fast multistep structure adapted multipole method) and evaluate its performance. In the second part we present, as a recent application of this method, an MD study of a ligand-receptor unbinding process enforced by single molecule atomic force microscopy. Through comparison of computed unbinding forces with experimental data we evaluate the quality of the simulations. The third part sketches, as a perspective, one way to drastically extend accessible time scales if one restricts oneself to the study of conformational transitions, which arc ubiquitous in proteins and are the elementary steps of many functional conformational motions. 

Atomic Force Microscopy Studies of Single DNA Molecules. 125... 

Camesano, T.A., and Wilkinson, K.J. (2001). Single molecule study of xanthan conformation using atomic force microscopy. Biomacromolecules, 2, 1184-1191. 

Fisher, T.E., Marszalek, P.E., Oberhauser, A.F., Carrion-Vazquez, M., and Fernandez, J.M. (1999). The micro-mechanics of single molecules studied with atomic force microscopy. J. Physiolo., 520, 5-14. 

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