Atomic reconstruction of biomolecular structures from AFM images and quantitative validation of experimental data using simulated AFM scanning

Abstract

We provide the BioAFMviewer-Toolbox, an extension of our previously developed software platform for simulated AFM scanning of biomolecular structures and dy- namics. The focus was on developing a toolbox of methods which employ simulated AFM scanning combined with quantitative analysis to facilitate the interpretation of resolution-limited AFM images. The key advancement is the automatized fitting of biomolecular structures to experimental AFM images, which allows to reconstruct 3D atomistic structures from AFM surface scans. Moreover, several methods for detailed analysis and comparison of surface topographies in simulated and experimental AFM images are provided. We demonstrate the applicability of the developed tools in the interpretation of high-speed AFM observations of proteins. The toolbox is implemented into the versatile interactive interface of the BioAFMviewer, which is a free software package available at www.bioafmviewer.com.

Simulation atomic force microscopy to predict correlated conformational dynamics in proteins from topographic imaging

“…Thus, a molecular movie of feasible conformational motions along the operation cycle of the MATE transporter was obtained (Supplementary Movie 1). This movie was processed by the BioAFMviewer software which performs simulation AFM to produce a computerized AFM experiment 9,10 . We conducted two in-silico AFM experiments of the MATE transporter operation cycle, scanning the extracellular and the intracelluar side, respectively.…”

“…We recently developed the BioAFMviewer software platform, which implements simulation atomic force microscopy (simAFM) of biomolecular structures and molecular movies of their conformational dynamics 9 . We further demonstrated how simAFM and automatized fitting to experimental images allow to reconstruct 3D atomic structures from AFM surface scans and enable quantitative molecular feature assignment within measured topographies 10 .…”

Envision and Appraisal of Biomolecules and Their Interactions through Scanning Probe Microscopy

“…[61] AFM shows a prominent feature over the STM that it can accept insulating surfaces in various conditions (e.g., buffer solution) and makes it attractive for studying biological molecules in approximate physiological conditions on a nanometer scale. [64,65] AFM is conventionally used to appraise the structural characteristics of various biological samples right from proteins [66] and nucleic acids [67,68] to living cells also. [69,70] Its acceptability in aqueous environments, as biomolecules show important activities only in aqueous conditions, facilitates it as a prime tool for real-time microbe monitoring.…”