Soojin Jo

Ternary and senary representations using DNA double-crossover tiles

The information capacity of DNA double-crossover (DX) tiles was successfully increased beyond a binary representation to higher base representations. By controlling the length and the position of DNA hairpins on the DX tile, ternary and senary (base-3 and base-6) digit representations were realized and verified by atomic force microscopy. Also, normal mode analysis was carried out to study the mechanical characteristics of each structure.

Fabrication and Characterization of Finite-Size DNA 2D Ring and 3D Buckyball Structures

In order to incorporate functionalization into synthesized DNA nanostructures, enhance their production yield, and utilize them in various applications, it is necessary to study their physical stabilities and dynamic characteristics. Although simulation-based analysis used for DNA nanostructures provides important clues to explain their self-assembly mechanism, structural function, and intrinsic dynamic characteristics, few studies have focused on the simulation of DNA supramolecular structures due to the structural complexity and high computational cost. Here, we demonstrated the feasibility of using normal mode analysis for relatively complex DNA structures with larger molecular weights, i.e., finite-size DNA 2D rings and 3D buckyball structures. The normal mode analysis was carried out using the mass-weighted chemical elastic network model (MWCENM) and the symmetry-constrained elastic network model (SCENM), both of which are precise and efficient modeling methodologies. MWCENM considers both the weight of the nucleotides and the chemical bonds between atoms, and SCENM can obtain mode shapes of a whole structure by using only a repeated unit and its connectivity with neighboring units. Our results show the intrinsic vibrational features of DNA ring structures, which experience inner/outer circle and bridge motions, as well as DNA buckyball structures having overall breathing and local breathing motions. These could be used as the fundamental basis for designing and constructing more complicated DNA nanostructures.

Normal mode analysis of Zika virus.

In recent years, Zika virus (ZIKV) caused a new pandemic due to its rapid spread and close relationship with microcephaly. As a result, ZIKV has become an obvious global health concern. Information about the fundamental viral features or the biological process of infection remains limited, despite considerable efforts. Meanwhile, the icosahedral shell structure of the mature ZIKV was recently revealed by cryo-electron microscopy. This structural information enabled us to simulate ZIKV. In this study, we analyzed the dynamic properties of ZIKV through simulation from the mechanical viewpoint. We performed normal mode analysis (NMA) for a dimeric structure of ZIKV consisting of the envelope proteins and the membrane proteins as a unit structure. By analyzing low-frequency normal modes, we captured intrinsic vibrational motions and defined basic vibrational properties of the unit structure. Moreover, we also simulated the entire shell structure of ZIKV at the reduced computational cost, similar to the case of the unit structure, by utilizing its icosahedral symmetry. From the NMA results, we can not only comprehend the putative dynamic fluctuations of ZIKV but also verify previous inference such that highly mobile glycosylation sites would play an important role in ZIKV. Consequently, this theoretical study is expected to give us an insight on the underlying biological functions and infection mechanism of ZIKV.

Vibrational characteristics of DNA nanostructures obtained through a mass-weighted chemical elastic network model

Using the programmable and self-assembly characteristics of DNA, various DNA nanostructures have been designed and synthesized for specific applications, such as nanomachinery and chemical/biological sensors. Although their physical features and feasibility in engineering applications can be conjectured using experimental techniques such as atomic force microscopy and Raman spectroscopy, their vibration characteristics at low frequency states, which are the most dominant factors that determine their structural functions, are difficult to observe experimentally because it is almost impossible to capture the real-time atomic motion of DNA nanostructures. Here, we propose a novel method to elucidate the vibration characteristics of DNA nanostructures in atomic detail using a normal mode analysis based on a mass-weighted chemical elastic network model (MWCENM). Because the MWCENM is a precise method for modeling molecular structures that considers both chemical bond information and inertia effects, it can calculate both vibration frequencies and the corresponding mode shapes in atomic detail. In terms of vibration frequencies, our simulation results show good agreement, within an error deviation of 4.0%, with experimental data measured by Raman spectroscopy. Therefore, the proposed theoretical approach is a feasible method for understanding DNA nanostructures vibration characteristics, including both frequencies and mode shapes, in atomic detail, adding to the molecular fingerprint provided by the conventional Raman spectrum.

Optimal Design of an Aquaporin Lipid Membrane System using Molecular Dynamics Simulation

orientation and flux through hAQP1 under PEFs, with voltage-dependent transport rates that diverge from diffusive and osmotic experiments. Surprisingly, hAQP1 was able to transport Cl anions (but not Na cations) when 1-2 volts was applied, despite its inability to do so under physiological conditions. The protein did not affect the construction of discrete lipid electropores around the periphery of the channel, or the timescales of lipid bilayer permeabilization, however a small reduction in the protein’s alpha-helicity was detected. hAQP1 Cl conduction was also sensitive to the protonation state of the histidine residue located in the two-stage filter, suggesting that pH may also affect anion conduction. Taken together, these results suggest that PEFs have a direct effect on transmembrane water channels, even before membrane electropores interact with them. Further studies of additional membrane components under PEFs are necessary if optimization of therapeutic electric fields is to be significantly improved.

Normal mode-guided transition pathway generation in proteins

The biological function of proteins is closely related to its structural motion. For instance, structurally misfolded proteins do not function properly. Although we are able to experimentally obtain structural information on proteins, it is still challenging to capture their dynamics, such as transition processes. Therefore, we need a simulation method to predict the transition pathways of a protein in order to understand and study large functional deformations. Here, we present a new simulation method called normal mode-guided elastic network interpolation (NGENI) that performs normal modes analysis iteratively to predict transition pathways of proteins. To be more specific, NGENI obtains displacement vectors that determine intermediate structures by interpolating the distance between two end-point conformations, similar to a morphing method called elastic network interpolation. However, the displacement vector is regarded as a linear combination of the normal mode vectors of each intermediate structure, in order to enhance the physical sense of the proposed pathways. As a result, we can generate more reasonable transition pathways geometrically and thermodynamically. By using not only all normal modes, but also in part using only the lowest normal modes, NGENI can still generate reasonable pathways for large deformations in proteins. This study shows that global protein transitions are dominated by collective motion, which means that a few lowest normal modes play an important role in this process. NGENI has considerable merit in terms of computational cost because it is possible to generate transition pathways by partial degrees of freedom, while conventional methods are not capable of this.

Dynamic characteristics of a flagellar motor protein analyzed using an elastic network model

At the base of a flagellar motor, its rotational direction and speed are regulated by the interaction between rotor and stator proteins. A switching event occurs when the cytoplasmic rotor protein, called C-ring, changes its conformation in response to binding of the CheY signal protein. The C-ring structure consists of FliG, FliM, and FliN proteins and its conformational changes in FliM and FliG including HelixMC play an important role in switching the motor direction. Therefore, clarifying their dynamic properties as well as conformational changes is a key to understanding the switching mechanism of the motor protein. In this study, to elucidate dynamic characteristics of the C-ring structure, both harmonic (intrinsic vibration) and anharmonic (transition pathway) analyses are conducted by using the symmetry-constrained elastic network model. As a result, the first three normal modes successfully capture the essence of transition pathway from wild type to CW-biased state. Their cumulative square overlap value reaches up to 0.842. Remarkably, it is also noted from the transition pathway that the cascade of interactions from the signal protein to FliM to FliG, highlighted by the major mode shapes from the first three normal modes, induces the reorientation (∼100° rotation of FliGC5) of FliG C-terminal that directly interacts with the stator protein. Presumably, the rotational direction of the motor protein is switched by this substantial change in the stator-rotor interaction.