Computation of topographic and three-dimensional atomic force microscopy images of biopolymers by calculating forces.

Atomic force microscopy (AFM) is widely utilized to visualize the molecular motions of biomolecules. Comparison of experimentally measured AFM images with simulated AFM images based on known structures of biomolecules is often necessary to elucidate what is actually resolved in the images. Experimental AFM images are generated by force measurements; however, conventional AFM simulation has been based on geometrical considerations rather than calculating forces using molecular dynamics simulations due to limited computation time. This letter summarizes recently developed methods to simulate topographic and three-dimensional AFM (3D-AFM) images of biopolymers such as chromosomes and cytoskeleton fibers. Scanning such biomolecules in AFM measurements usually results in nonequilibrium-type work being performed. As such, the Jarzynski equality was employed to relate the nonequilibrium work to the free energy profiles, and the forces were calculated by differentiating the free energy profiles. The biomolecules and probes were approximated using a supra-coarse-grained model, allowing the simulation of force-distance curves in feasible time. It was found that there is an optimum scanning velocity and that some of polymer structures are resolved in the simulated 3D-AFM images. The theoretical background adopted to rationalize the use of small probe radius in the conventional AFM simulation of biomolecules is clarified.