scholarly journals Flexible Fitting of Biomolecular Structures to Atomic Force Microscopy Images via Biased Molecular Simulations

2019 ◽  
Author(s):  
Toru Niina ◽  
Sotaro Fuchigami ◽  
Shoji Takada
Keyword(s):  
Atomic Force Microscopy ◽  
Rigid Body ◽  
Protein Structures ◽  
Three Dimensional ◽  
Molecular Structures ◽  
Surface Shape ◽  
Dimensional Structure ◽  
Force Microscopy ◽  
Atomic Force ◽  
Afm Image

AbstractAtomic force microscopy (AFM) is a prominent imaging technology that observes large-scale structural dynamics of biomolecules near the physiological condition, but the AFM data are limited to the surface shape of specimens. Rigid-body fitting methods were developed to obtain molecular structures that fit to an AFM image, without accounting for conformational changes. Here we developed a method to fit flexibly a three-dimensional biomolecular structure into an AFM image. First, we describe a method to produce a pseudo-AFM image from a given three-dimensional structure in a differentiable form. Then, using a correlation function between the experimental AFM image and the computational pseudo-AFM image, we developed a flexible fitting molecular dynamics (MD) simulation method, by which we obtain protein structures that well fit to the given AFM image. We first test it with a twin-experiment; for a synthetic AFM image produced from a protein structure different from its native conformation, the flexible fitting MD simulations sampled those that fit well the AFM image. Then, parameter dependence in the protocol is discussed. Finally, we applied the method to a real experimental AFM image for a flagellar protein FlhA, demonstrating its applicability. We also test the rigid-body fitting of a fixed structure to the AFM image. Our method will be a general tool for structure modeling based on AFM images and is publicly available through CafeMol software.

scholarly journals Rigid-body fitting to atomic force microscopy images for inferring probe shape and biomolecular structure

2021 ◽  
Vol 17 (7) ◽  
pp. e1009215
Author(s):  
Toru Niina ◽  
Yasuhiro Matsunaga ◽  
Shoji Takada
Keyword(s):  
Atomic Force Microscopy ◽  
Rigid Body ◽  
Correlation Coefficient ◽  
High Speed ◽  
Similarity Score ◽  
Molecular Structures ◽  
Cosine Similarity ◽  
Force Microscopy ◽  
Atomic Force ◽  
Dynamics Simulations

Atomic force microscopy (AFM) can visualize functional biomolecules near the physiological condition, but the observed data are limited to the surface height of specimens. Since the AFM images highly depend on the probe tip shape, for successful inference of molecular structures from the measurement, the knowledge of the probe shape is required, but is often missing. Here, we developed a method of the rigid-body fitting to AFM images, which simultaneously finds the shape of the probe tip and the placement of the molecular structure via an exhaustive search. First, we examined four similarity scores via twin-experiments for four test proteins, finding that the cosine similarity score generally worked best, whereas the pixel-RMSD and the correlation coefficient were also useful. We then applied the method to two experimental high-speed-AFM images inferring the probe shape and the molecular placement. The results suggest that the appropriate similarity score can differ between target systems. For an actin filament image, the cosine similarity apparently worked best. For an image of the flagellar protein FlhAC, we found the correlation coefficient gave better results. This difference may partly be attributed to the flexibility in the target molecule, ignored in the rigid-body fitting. The inferred tip shape and placement results can be further refined by other methods, such as the flexible fitting molecular dynamics simulations. The developed software is publicly available.

scholarly journals The Use of Atomic Force Microscopy for 3D Analysis of Nucleic Acid Hybridization on Microarrays

Acta Naturae ◽  
2015 ◽  
Vol 7 (2) ◽  
pp. 108-114 ◽  
Author(s):  
E. V. Dubrovin ◽  
G. V. Presnova ◽  
M. Yu. Rubtsova ◽  
A. M. Egorov ◽  
V. G Grigorenko ◽  
...  
Keyword(s):  
Atomic Force Microscopy ◽  
Nucleic Acids ◽  
Detection Threshold ◽  
Three Dimensional ◽  
Quantitative Measure ◽  
Nucleic Acid Hybridization ◽  
Dimensional Structure ◽  
3D Analysis ◽  
Force Microscopy ◽  
Atomic Force

Oligonucleotide microarrays are considered today to be one of the most efficient methods of gene diagnostics. The capability of atomic force microscopy (AFM) to characterize the three-dimensional morphology of single molecules on a surface allows one to use it as an effective tool for the 3D analysis of a microarray for the detection of nucleic acids. The high resolution of AFM offers ways to decrease the detection threshold of target DNA and increase the signal-to-noise ratio. In this work, we suggest an approach to the evaluation of the results of hybridization of gold nanoparticle-labeled nucleic acids on silicon microarrays based on an AFM analysis of the surface both in air and in liquid which takes into account of their three-dimensional structure. We suggest a quantitative measure of the hybridization results which is based on the fraction of the surface area occupied by the nanoparticles.

scholarly journals Rigid-body fitting to atomic force microscopy images for inferring probe shape and biomolecular structure

2021 ◽  
Author(s):  
Toru Niina ◽  
Yasuhiro Matsunaga ◽  
Shoji Takada
Keyword(s):  
Atomic Force Microscopy ◽  
Rigid Body ◽  
Real Time ◽  
High Speed ◽  
Surface Shape ◽  
Time Dynamics ◽  
Force Microscopy ◽  
Small Proteins ◽  
Atomic Force ◽  
Functional Dynamics

AbstractHigh-speed (HS) atomic force microscopy (AFM) can visualize real-time dynamics of functional biomolecules near the physiological condition, but the observed data are limited to the surface height of specimens. Since the HS-AFM images highly depend on the probe tip shape, for successful inference of molecular structures from the measurement, the knowledge of the probe shape is required, but is often missing. Here, we developed a method of the rigid-body fitting to HS-AFM images, which simultaneously finds the shape of the probe tip and the placement of the molecular structure via an exhaustive search. We examined four similarity scores via twin-experiments for four test proteins: Of the four scores, the cosine similarity generally worked best, whereas the pixel-RMSD was also useful especially for the placement of small proteins. We then applied the method to two experimental HS-AFM images inferring the probe shape and the molecular placement. The inferred tip shape and placement results can be further refined by other methods, such as the flexible fitting molecular dynamics simulations. The developed software is publicly available.Author SummaryObservation of functional dynamics of individual biomolecules is important to understand molecular mechanisms of cellular phenomena. High-speed (HS) atomic force microscopy (AFM) is a powerful tool that enables us to visualize the real-time dynamics of working biomolecules under near-physiological conditions. However, the information available by the HS-AFM images is limited to the two-dimensional surface shape detected via the force to the probe. While the surface information is affected by the shape of the probe tip, the probe shape itself cannot be directly measured before each HS-AFM measurement. To overcome this problem, we have developed a computational method to simultaneously infer the probe tip shape and the molecular placement from an HS-AFM image. We show that our method successfully estimates the effective HS-AFM tip shape and visualizes a structure with a more accurate placement. The estimation of a molecular placement with the correct probe tip shape enables us to obtain more insights into functional dynamics of the molecule from HS-AFM images.

Three Dimensional Structure of Human Fibrinogen under Aqueous Conditions Visualized by Atomic Force Microscopy

1997 ◽  
Vol 77 (06) ◽  
pp. 1048-1051 ◽  
Author(s):  
Roger E Marchant ◽  
Matthew D Barb ◽  
John R Shainoff ◽  
Steven J Eppell ◽  
David L Wilson ◽  
...  
Keyword(s):  
Atomic Force Microscopy ◽  
Three Dimensional ◽  
Hydrophobic Surface ◽  
Dimensional Structure ◽  
Structure And Properties ◽  
Human Fibrinogen ◽  
Force Microscopy ◽  
Atomic Force ◽  
Molecular Scale ◽  
Aqueous Conditions

SummaryFibrinogen plays a central role in surface-induced thrombosis. However, the interactions of fibrinogen with different substrata remain poorly understood because of the difficulties involved in imaging globular proteins under aqueous conditions. We present detailed three dimensional molecular scale images of fibrinogen molecules on a hydrophobic surface under aqueous conditions obtained by atomic force microscopy. Hydrated fibrinogen monomers are visualized as overlapping ellipsoids; dimers and trimers have linear conformations predominantly, and increased affinity for the hydrophobic surface compared with monomeric fibrinogen. The results demonstrate the importance of hydration on protein structure and properties that affect surface-dependent interactions.

scholarly journals Acoustic subsurface-atomic force microscopy: Three-dimensional imaging at the nanoscale

2021 ◽  
Vol 129 (3) ◽  
pp. 030901
Author(s):  
Hossein J. Sharahi ◽  
Mohsen Janmaleki ◽  
Laurene Tetard ◽  
Seonghwan Kim ◽  
Hamed Sadeghian ◽  
...  
Keyword(s):  
Atomic Force Microscopy ◽  
Three Dimensional ◽  
Three Dimensional Imaging ◽  
Force Microscopy ◽  
Atomic Force
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