Journal of Computer Chemistry, Japan
Online ISSN : 1347-3824
Print ISSN : 1347-1767
ISSN-L : 1347-1767
Volume 17 , Issue 1
Special Issue: Computer Chemistry in Dynamical Ordering of Biomolecular Systems for Creation of Integrated Functions
Showing 1-12 articles out of 12 articles from the selected issue
Foreword
Account
  • Takumi YAMAGUCHI, Tokio WATANABE, Hirokazu YAGI, Koichi KATO
    2018 Volume 17 Issue 1 Pages 1-7
    Published: 2018
    Released: March 23, 2018
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    Oligosaccharides are highly flexible molecules having branched structures and significant degrees of freedom in internal motion. To gain insights into the molecular basis of their biological functions, it is essential to describe the conformational dynamics of oligosaccharides. By combining NMR spectroscopy and molecular simulation, we developed a method giving the quantitative interpretation of dynamic behaviors of oligosaccharides. Paramagnetism-assisted NMR approaches with replica-exchange molecular dynamics simulations revealed the conformations of a series of oligosaccharides involved in the glycoprotein quality control system in cells. Exploration of the conformational spaces of the oligosaccharides also provided dynamical views of the interaction mechanisms of carbohydrate recognition proteins, complementing the static crystallographic analyses.

  • Hideyoshi MOTOKI, Norio YOSHIDA, Shun HIROTA, Masahiro HIGASHI
    2018 Volume 17 Issue 1 Pages 8-13
    Published: 2018
    Released: March 23, 2018
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    Cytochrome c is a hemoprotein that plays an important role in electron transport in the mitochondrial respiratory chain. Cytochrome c forms oligomers by successive domain swapping, where the C-terminal α helices are replaced by the corresponding helices of other cytochrome c molecules, leading to a loss in the electron transfer function. However, the detailed mechanism of domain swapping of cytochrome c is still unclear. To clarify the mechanism of the oligomerization, we have analyzed the thermodynamic stabilities of the domain-swapped dimer. In this paper, we introduce our recent progress.

  • Ryoichi YAMAMOTO, John J. MOLINA, Simon K. SCHNYDER
    2018 Volume 17 Issue 1 Pages 14-19
    Published: 2018
    Released: March 23, 2018
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    The motion of cells is extremely complex and crucial for the function of biological systems [1]. Understanding how cells interact with each other to collectively move could prove extremely valuable, and has attracted the attention of many researchers in the fields of biology, medicine, and physics. Those researchers try to construct cell models that are simple but able to reproduce many complex cell behaviors [2-12]. The authors proposed a minimal model which represents cells as two disks connected by a spring, one for the pseudopod (the front of the cell) and the other one for the cell body [13] (See Figure1). By coupling the pseudopod's motility to the extension of the spring, they found that cells naturally exhibit contact inhibition of locomotion (CIL), i.e. they slow down and change direction upon contact, and arrest at high cell densities. Furthermore, they found that the shape of the cell greatly influences collective motion. Most importantly, cells with a large front quickly align their motion, suggesting that cells might have evolved broader fronts to facilitate alignment [13] (See Figure2). The model is further extended to include the process of cell division and the contact inhibition of proliferation (CIP) of cells.

Review
  • Takayuki UCHIHASHI
    2018 Volume 17 Issue 1 Pages 20-30
    Published: 2018
    Released: March 23, 2018
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    Recent progress of high-speed atomic force microscopy (HS-AFM) has enabled us to visualize dynamic conformational change and molecular interaction of proteins in realtime under a physiological condition. Molecular mechanisms through dynamic phenomena that have been deduced from the accumulation of experimental evidence by various analytical techniques are now able to be directly and intuitively understood from AFM movies. While a movie provides a great deal of information compared to a static image, extracting useful information based on objective criteria is essential for the next step. This review describes representative HS-AFM data for three typical dynamic biological phenomena; conformational dynamics of single proteins, linear movement of enzymes and velocity analysis and dynamic molecular interaction together with imaging processing techniques for interpreting AFM data and efficient analysis of successive images.

  • Takako MASHIKO, Shuichi HIRAOKA, Umpei NAGASHIMA, Masanori TACHIKAWA
    2018 Volume 17 Issue 1 Pages 31-37
    Published: 2018
    Released: March 23, 2018
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    Gear-shaped amphiphile (GSA) molecules 1(R=CH3), recently synthesized by Hiraoka et al., are self-assembled into a hexameric structure of nanocube (16) in 25% aqueous methanol solvent. Meanwhile, demethylated GSA molecules 2(R=H) are not self-assembled into nanocube (26), and both GSA 1 and GSA 2 are not self-assembled in pure methanol solvent. To elucidate the detailed mechanism of the stability of these hexameric capsules (16 and 26) in several solvents such as water, 25% aqueous methanol, and methanol, we have carried out molecular dynamic (MD) simulations for these systems. Our MD results indicate that the so-called CH-π chain plays an important role for the stability of nanocubes 16. Methanol molecules improve solubility to form micelles with nanocubes, while the CH-π chain is broken by methanol molecules.

  • Chihong SONG, Kazuyoshi MURATA
    2018 Volume 17 Issue 1 Pages 38-45
    Published: 2018
    Released: March 23, 2018
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    As a new method for determining the structure of proteins, single particle structure analysis by cryo-electron microscopy has attracted attention. This method has less restrictions on samples, thus covering specimens with a wide molecular mass from small protein complexes of tens of kilo Daltons to large virus particles of several hundred mega Daltons in the same procedure (Figure 1). In addition, the spatial degree of freedom makes it possible to analyze dynamic structural changes and kinetics of proteins. In this review, we explain the principle of single particle structure analysis of cryo-electron microscopy, progress of image recording apparatus, and analysis methods making these possible, and also introduce applications to dynamic protein structure analysis.

  • Ryuhei HARADA, Yasuteru SHIGETA
    2018 Volume 17 Issue 1 Pages 46-56
    Published: 2018
    Released: March 23, 2018
    [Advance publication] Released: March 13, 2018
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    Several biological functions are strongly related to structural transitions of proteins indicating that one must analyze the relationship between dynamical ordering of proteins and related functions. These structural transitions are induced as slow dynamics upon collective motions including biologically relevant large-amplitude fluctuations of proteins. Although molecular dynamics (MD) simulation has become a powerful tool for reproducing the structural transitions of proteins, it might still be difficult to reach time scales of the biological functions, since the accessible time scale of conventional MD (CMD) simulation is far from them. To tackle the timescale issue of the CMD simulation, we developed several efficient conformational sampling methods based on a strategy of cascade-type MD. In the present review, we describe recent developments of our scheme and applications to proteins associated with several biologically relevant phenomena.

General Paper
  • Hironari KAMIKUBO
    2018 Volume 17 Issue 1 Pages 57-64
    Published: 2018
    Released: March 26, 2018
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    Various protein molecules concert with each other to express diverse biological functions. Because these multicomponent biological molecules weakly interact with each other, they can undergo regulatory dissociation and association upon inducing biological stimuli. In order to understand biological systems, we must, at first, aim to identify every possible unstable complex involved in the given multicomponent system, and then quantitatively analyze the interactions of these complex molecules. However, because of the complexity, it is generally difficult to apply conventional analytical methods to analyze such multi-component equilibrium systems. We have developed a new analytical device that would enable us to perform structure and interaction analyses on multi-component equilibrium systems. Here, I would like to introduce the description of the device and its potential applications of this sampling system applied for continuous titration SAXS method.

  • Teppei IKEYA, Yutaka ITO
    2018 Volume 17 Issue 1 Pages 65-75
    Published: 2018
    Released: March 26, 2018
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    Nuclear Magnetic Resonance (NMR) spectroscopy is the only tool to investigate the three-dimensional (3D) structures and dynamics of biomacromolecules at atomic resolution, in solution or in more natural environments such as living cells. On the other hand, since NMR data are principally only peak signals from atomic nuclei and often with imperfections and uncertainty, structural information must be properly extracted from the signals to build 3D conformations by NMR structure calculation. In NMR spectra of unstable or inhomogeneous samples, data become more sparse due to their low signal-to-noise ratio, making it difficult to determine accurate 3D structures. In order to more efficiently analyze the data, Rieping et al. proposed a new structure calculation method based on Bayes' theorem. We modified this approach in the CYANA program, allowing us to deduce the posterior probability of molecular ensembles with prior distributions, based on the Amber physical force field as well as on empirical knowledge, and to automate unambiguous and ambiguous NOE cross peak assignments. The sampling scheme for obtaining posterior probability is performed by a hybrid Monte Carlo algorithm, combined with Markov chain Monte Carlo (MCMC) by the Gibbs sampler, and a molecular dynamics simulation (MD) for collecting a canonical ensemble of conformations. Since it is not trivial to search the entire function space particularly for exploring the conformational prior due to the extraordinarily large conformation space of proteins, we perform the replica exchange method, in which several MCMC calculations with different temperatures are run in parallel as replicas. Simulated data and randomly deleted experimental peaks show that this new structure calculation method can provide accurate structures even with fewer peaks than the conventional method. We expect that solution NMR with our method will be a useful technique for the study of the”dynamical ordering” of biomacromolecules.

  • Hiroaki NISHIZAWA, Hisashi OKUMURA
    2018 Volume 17 Issue 1 Pages 76-79
    Published: 2018
    Released: March 26, 2018
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    Metal ions such as those of copper and zinc are considered to accelerate initial formation of amyloid fibril of amyloid-β (Aβ) peptides. In this study, the role of a zinc ion for Aβ peptide aggregation was investigated by the classical molecular dynamics (MD) simulations. The MD results indicated that the negatively-charged residues gained large stabilization in the existence of a zinc ion. On the other hand, histidine and tyrosine which were reported as making a bond with a metal ion were slightly stabled. Therefore, a zinc ion is thought of as combining with histidine or tyrosine after being attracted by negatively-charged residues, because these residues exist near negatively-charged residues. These results indicate that the metal-containing system needs to be treated by quantum-mechanical techniques.

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