• Proceedings of the Korean Society for Noise and Vibration Engineering Conference
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• 2008.04a
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• pp.476-479
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• 2008

Understanding the dynamics of proteins is essential to gain insight into biological functions of proteins. The protein dynamics is delineated by conformational fluctuation (i.e. thermal vibration), and thus, thermal vibration of proteins has to be understood. In this paper, a simple mechanical model was considered for understanding protein's dynamics. Specifically, a mechanical vibration model was developed for understanding the large protein dynamics related to biological functions. The mechanical model for large proteins was constructed based on simple elastic model (i.e. Tirion's elastic model) and model reduction methods (dynamic model condensation). The large protein structure was described by minimal degrees of freedom on the basis of model reduction method that allows one to transform the refined structure into the coarse-grained structure. In this model, it is shown that a simple reduced model is able to reproduce the thermal fluctuation behavior of proteins qualitatively comparable to original molecular model. Moreover, the protein's dynamic behavior such as collective dynamics is well depicted by a simple reduced mechanical model. This sheds light on that the model reduction may provide the information about large protein dynamics, and consequently, the biological functions of large proteins.

• Rapid Communication in Photoscience
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• v.4 no.1
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• pp.1-8
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• 2015

For understanding molecular mechanisms of photochemical reactions, in particular reactions of proteins with biological functions, it is important to elucidate both the initial reactions from the photoexcited states and the series of subsequent chemical reactions, e.g., conformation, intermolecular interactions (hydrogen bonding, hydrophobic interactions), and inter-protein interactions (oligomer formation, dissociation reactions). Although time-resolved detection of such dynamics is essential, these dynamics have been very difficult to track by traditional spectroscopic techniques. Here, relatively new approaches for probing the dynamics of protein photochemical reactions using time-resolved transient grating (TG) are reviewed. By using this method, a variety of spectrally silent dynamics can be detected and such data provide a valuable description about the reaction scheme. Herein, a blue light sensor protein TePixD is the exemplar. The initial photochemistry for TePixD occurs around the chromophore and is detected readily by light absorption, but subsequent reactions are spectrally silent. The TG experiments revealed conformational changes and changes in inter-protein interactions, which are essential for TePixD function. The TG experiments also showed the importance of fluctuations of the intermediates as the driving force of the reaction. This technique is complementary to optical absorption detection methods. The TG signal contains a variety of unique information, which is difficult to obtain by other methods. The advantages and methods for signal analyses are described in detail in this review.

• Bulletin of the Korean Chemical Society
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• v.29 no.11
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• pp.2172-2182
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• 2008

• Bulletin of the Korean Chemical Society
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• v.35 no.6
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• pp.1713-1719
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• 2014

1FSD is a 28-residue designed protein with a ${\beta}{\beta}{\alpha}$ motif. Since this protein displays most essential features of protein structures in such a small size, this model protein can be an outstanding system for evaluating the balance in the propensity of the secondary structures and the quality of all-atom protein force fields. Particularly, this protein would be difficult to fold to its correct native structure without establishing proper balances between the secondary structure elements in all-atom energy functions. In this work, a series of the recently optimized five amber protein force fields [$ff03^*$, $f99sb^*$-ildn, ff99sb-${\phi}^{\prime}$-ildn, ff99sb-nmr1-ildn, ff99sb-${\Phi}{\Psi}$(G24, CS)-ildn] were investigated for the simulations of 1FSD using a conventional molecular dynamics (MD) and a biased-exchange meta-dynamics (BEMD) methods. Among those tested force fields, we found that ff99sb-nmr1-ildn and ff99sb-${\Phi}{\Psi}$(G24, CS)-ildn are promising in that both force fields can locate the native state of 1FSD with a high accuracy (backbone rmsd ${\leq}1.7{\AA}$) in the global free energy minimum basin with a reasonable energetics conforming to a previous circular dichroism (CD) experiment. Furthermore, both force fields led to a common set of two distinct folding pathways with a heterogeneous nature of the transition state to the folding. We anticipate that these force fields are reasonably well balanced, thereby transferable to many other protein folds.

• Journal of Photoscience
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• v.9 no.2
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• pp.134-137
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• 2002

PYP consists of a water-soluble apoprotein and 4-hydroxycinnamyl chromophore bound to Cys69 via thiolester linkage, Upon absorption of a photon, the photocycle is initiated, leading to formation of several photo-intermediates. Among them, M intermediate is important to understand the signal transduction mechanism of PYP, because it is a putative signaling state. As well known, the dynamics of a protein is closely correlated with the occurrence of its function. Here we report the results of IO ns molecular dynamics (MD) simulation for the M intermediate in aqueous solution and discuss the characteristic feature of this state from a viewpoint of structural fluctuation.

• Molecules and Cells
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• v.42 no.12
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• pp.840-849
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• 2019

The spatiotemporal mitotic processes are controlled qualitatively by phosphorylation and qualitatively by ubiquitination. Although the SKP1-CUL1-F-box protein (SCF) complex and the anaphase-promoting complex/cyclosome (APC/C) mainly mediate ubiquitin-dependent proteolysis of mitotic regulators, the E3 ligase for a large portion of mitotic proteins has yet to be identified. Here, we report c-Cbl as an E3 ligase that degrades DDA3, a protein involved in spindle dynamics. Depletion of c-Cbl led to increased DDA3 protein levels, resulting in increased recruitment of Kif2a to the mitotic spindle, a concomitant reduction in spindle formation, and chromosome alignment defects. Furthermore, c-Cbl depletion induced centrosome over-duplication and centriole amplification. Therefore, we concluded that c-Cbl controls spindle dynamics and centriole duplication through its E3 ligase activity against DDA3.

• BMB Reports
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• v.29 no.4
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• pp.380-385
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• 1996

Ovomucoid third domain is a serine proteinase inhibitor protein which consists of 56 amino acid residues. A fifty picosecond molecular dynamics (MD) simulation was carried out for ovomucoid third domain protein with 5 $\AA$ layer of water molecules. A comparison of main chain atoms in the MD averaged structure with the crystal structure showed that most of the backbone structures are maintained during the simulation. Investigation of the intramolecular hydrogen bondings indicated that most of the interactions between main chain atoms were conserved, whereas those between side chains were reorganized for the period of the simulation. Especially, the side chain interactions around the scissile bond of reactive site P1 (Met18) were found to be more extensive for the MD structures. During the simulation, hydrogen bonds were maintained between the side chains of Glu19 and Arg21 as well as those of Thr17 and Glu19. Extensive side chain interactions observed in the MD structures may shed light on the question of why protein proteinase inhibitors are strong inhibitors for proteinases rather than good substrates.

• Proceeding of EDISON Challenge
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• 2015.03a
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• pp.70-75
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• 2015

Fasciclin 1 (FAS1) is an extracellular protein whose aggregation in cornea leads to visual impairment. While a number of FAS1 mutants have been studied that exhibit enhanced/decreased aggregation propensity, no structural information has been provided so far that is associated with distinct aggregation potential. In this study, we have investigated the structural and thermodynamic characteristics of the wild-type FAS1 and its two mutants, R555Q and R555W, by using molecular dynamics simulations and three-dimensional reference interaction site model (3D-RISM) theory. We find that the hydrophobic solvent accessible surface area increases due to hydrophobic core repacking in the C-terminus caused by the mutation. We also find that the solvation free energy of the mutants increases due to the enhanced non-native H-bonding. These structural and thermodynamic changes upon mutation contribute to understand the aggregation of these mutants.

• Proceedings of the Korean Vacuum Society Conference
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• 2011.02a
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• pp.21-21
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• 2011

A series of Quasi-Elastic Neutron Scattering (QENS) experiments helps us to understand the single-particle (hydrogen atom) dynamics of a globular protein and its hydration water and strong coupling between them. We also performed Molecular Dynamics (MD) simulations on a realistic model of the hydrated hen-egg Lysozyme powder having two proteins in the periodic box. We found the existence of a Fragile-to-Strong dynamic Crossover (FSC) phenomenon in hydration water around a protein occurring at TL=$225{\pm}5K$ by analyzing Intermediate Scattering Function (ISF). On lowering of the temperature toward FSC, the structure of hydration water makes a transition from predominantly the High Density Liquid (HDL) form, a more fluid state, to predominantly the Low Density Liquid (LDL) form, a less fluid state, derived from the existence of a liquid?liquid critical point at an elevated pressure. We showed experimentally and confirmed theoretically that this sudden switch in the mobility of the hydration water around a protein triggers the dynamic transition (so-called glass transition) of the protein, at a temperature TD=220 K. Mean Square Displacement (MSD) is the important factor to show that the FSC is the key to the strong coupling between a protein and its hydration water by suggesting TL${\fallingdotseq}$TD. MD simulations with TIP4P force field for water were performed to understand hydration level dependency of the FSC temperature. We added water molecules to increase hydration level of the protein hydration water, from 0.30, 0.45, 0.60 and 1.00 (1.00 is the bulk water). These confirm the existence of the FSC and the hydration level dependence of the FSC temperature: FSC temperature is decreased upon increasing hydration level. We compared the hydration water around Lysozyme, B-DNA and RNA. Similarity among those suggests that the FSC and this coupling be universal for globular proteins, biopolymers.

• Bulletin of the Korean Chemical Society
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• v.32 no.10
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• pp.3553-3554
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• 2011