Flexible Fitting of Biomolecular Structures to Atomic Force Microscopy Images via Biased Molecular Simulations
Autor: | Toru Niina, Sotaro Fuchigami, Shoji Takada |
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Rok vydání: | 2020 |
Předmět: |
Materials science
Protein Conformation Biomolecular structure Molecular Dynamics Simulation Microscopy Atomic Force 01 natural sciences Image (mathematics) Quantitative Biology::Subcellular Processes Molecular dynamics Software Fitting methods 0103 physical sciences Native state Physical and Theoretical Chemistry chemistry.chemical_classification 010304 chemical physics Atomic force microscopy business.industry Biomolecule Proteins Sample (graphics) Computer Science Applications Correlation function (statistical mechanics) Models Chemical chemistry Condensed Matter::Strongly Correlated Electrons business Biological system Monte Carlo Method |
Zdroj: | Journal of Chemical Theory and Computation. 16:1349-1358 |
ISSN: | 1549-9626 1549-9618 |
DOI: | 10.1021/acs.jctc.9b00991 |
Popis: | High-speed (HS) atomic 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 (3D) biomolecular structure into an AFM image. First, we describe a method to produce a pseudo-AFM image from a given 3D 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; using an AFM image produced from a protein structure different from its native conformation as a reference, we performed the flexible fitting MD simulations to sample conformations that fit well the reference AFM image, and the method was confirmed to work well. Then, parameter dependence in the protocol was discussed. Finally, we applied the method to a real experimental HS-AFM image for a flagellar protein FlhA, demonstrating its applicability. We also test the rigid-body fitting of a molecular structure to an AFM image. Our method will be a general tool for dynamic structure modeling based on HS-AFM images and is publicly available through the CafeMol software. |
Databáze: | OpenAIRE |
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