• Advances in Computational Design
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• v.3 no.2
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• pp.147-163
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• 2018

Cementitious composites are multiphase heterogeneous materials with distinct dissimilarity in strength under compression and tension (high under compression and very low under tension). At macro scale, the phenomenon can be well-explained as the material contains physical heterogeneity and pores. But, it is interesting to note that this dissimilarity initiates at molecular level where there is no heterogeneity. In this regard, molecular dynamics based computational investigations are carried out on cement clinkers and calcium silicate hydrate (C-S-H) under tension and compression to trace out the origin of dissimilarity. In the study, effect of strain rate, size of computational volume and presence of un-structured atoms on the obtained response is also investigated. It is identified that certain type of molecular interactions and the molecular structural parameters are responsible for causing the dissimilarity in behavior. Hence, the judiciously modified or tailored molecular structure would not only be able to reduce the extent of dissimilarity, it would also be capable of incorporating the desired properties in heterogeneous composites. The findings of this study would facilitate to take step to scientifically alter the structure of cementitious composites to attain the desired mechanical properties.

• Macromolecular Research
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• v.17 no.12
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• pp.976-986
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• 2009

With the study goal of firstly elucidating the anisotropic interactions between oriented polymer chain segments and liquid crystal (LC) molecules, and secondly of determining the contributions of the chemical components of the polymer segments to the film surface topography, LC alignment, pretilt, and anchoring energy, we synthesized three dianhydrides, 1,4-bis(4'-t-butylphenyl)pyromellitic dianhydride (BBPD), 1,4-bis(4'-trimethylsilylphenyl)pyromellitic dianhydride(BTPD), and 2,2'-bis(4"-tert-butylphenyl)-4,4',5,5'-biphenyltetracarboxylic dianhydride (BBBPAn), and a series of their organosoluble polyirnides, BBPD-ODA, BBPD-MDA, BBPD-FDA, BTPD-FDA, and BBBPAn-FDA, which contain the diamines 4,4'-oxydianiline (ODA), 4,4'-methylenediamine (MDA), and 4,4'-(hexafluoroisopropylidene)dianiline (FDA). All the polyimides were determined to be positive birefringent polymers, regardless of the chemical components. Although all the rubbed polyimide films exhibited microgrooves which were created by rubbing process, the film surface topography varied depending on the polyimides. In all the rubbed films, the polymer chains were unidirectionally oriented along the rubbing direction. However, the degree of in-plane birefringence in the rubbed film varied depending on the polyimides. The rubbing-aligned polymer chains in the polyimide films effectively induced the alignment of nematic LCs along their orientation directors by anisotropic interactions between the preferentially oriented polymer chain segments and the LCs. The azimuthal and polar anchoring energies of the LCs ranged from $0.45{\times}10^{-4}\;-\;1.37{\times}10^{-4}\;J/m^2$ and from $0.86{\times}10^{-5}\;-\;4.26{\times}10^{-5}\;J/m^2$, respectively, depending on the polyimides. The pretilt angles of the LCs were in the range $0.10-0.62^{\circ}$. In summary, the soluble aromatic polyimides reported here are promising LC alignment layer candidates for the production of advanced LC display devices.

• Molecules and Cells
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• v.27 no.3
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• pp.271-277
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• 2009

Proteins interact with each other within a cell, and those interactions give rise to the biological function and dynamical behavior of cellular systems. Generally, the protein interactions are temporal, spatial, or condition dependent in a specific cell, where only a small part of interactions usually take place under certain conditions. Recently, although a large amount of protein interaction data have been collected by high-throughput technologies, the interactions are recorded or summarized under various or different conditions and therefore cannot be directly used to identify signaling pathways or active networks, which are believed to work in specific cells under specific conditions. However, protein interactions activated under specific conditions may give hints to the biological process underlying corresponding phenotypes. In particular, responsive functional modules consist of protein interactions activated under specific conditions can provide insight into the mechanism underlying biological systems, e.g. protein interaction subnetworks found for certain diseases rather than normal conditions may help to discover potential biomarkers. From computational viewpoint, identifying responsive functional modules can be formulated as an optimization problem. Therefore, efficient computational methods for extracting responsive functional modules are strongly demanded due to the NP-hard nature of such a combinatorial problem. In this review, we first report recent advances in development of computational methods for extracting responsive functional modules or active pathways from protein interaction network and microarray data. Then from computational aspect, we discuss remaining obstacles and perspectives for this attractive and challenging topic in the area of systems biology.

• Molecules and Cells
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• v.43 no.11
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• pp.899-908
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• 2020

Intrinsically disordered proteins or regions (IDPs or IDRs) are widespread in the eukaryotic proteome. Although lacking stable three-dimensional structures in the free forms, IDRs perform critical functions in various cellular processes. Accordingly, mutations and altered expression of IDRs are associated with many pathological conditions. Hence, it is of great importance to understand at the molecular level how IDRs interact with their binding partners. In particular, discovering the unique interaction features of IDRs originating from their dynamic nature may reveal uncharted regulatory mechanisms of specific biological processes. Here we discuss the mechanisms of the macromolecular interactions mediated by IDRs and present the relevant cellular processes including transcription, cell cycle progression, signaling, and nucleocytoplasmic transport. Of special interest is the multivalent binding nature of IDRs driving assembly of multicomponent macromolecular complexes. Integrating the previous theoretical and experimental investigations, we suggest that such IDR-driven multiprotein complexes can function as versatile allosteric switches to process diverse cellular signals. Finally, we discuss the future challenges and potential medical applications of the IDR research.

• Bulletin of the Korean Chemical Society
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• v.29 no.8
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• pp.1499-1504
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• 2008

Pyrazine derivatives bind to b-RAF receptor which is important in cancer therapy. The ligand-receptor interactions have been studied by comparative molecular field analysis (CoMFA) and molecular docking methods. Applying conventional ligand-based alignment schemes for the whole set was not successful. However, QM and DFT results suggested that some ligands have electrostatic interaction while others have steric interactions. On the basis of these results, we divided the dataset into two subsets. Electrostatic effect was found to be important in one set while steric effect for the other. Best docking modes were obtained for each subset based on the available crystal structure. These receptor-guided CoMFA models propose an interesting possibility which is difficult to obtain otherwise. i.e., in one binding mode the electrostatic interaction plays a key role for one subset ($q^2$ = 0.46, $r^2$ = 0.98), while in another binding mode steric effect is important with another subset ($q^2$ = 0.43, $r^2$ = 0.74).

• Journal of the Korean Magnetic Resonance Society
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• v.1 no.2
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• pp.112-125
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• 1997

It has been demonstrated that mutant Hemoglobins (Hb) which have an altered ${\alpha}$1${\beta}$2 subunit interface can be designed. A compensatory mutation for a naturally occurring abnormal human Hb, Hb Kempsey (${\beta}$99Asp\longrightarrowAsn), has been designed, and this mutation allowed the molecule to regain its allosteric response. The calculated values for the difference in the free energy of cooperativity show excellent agreement with experimentally determined thermodynamic values, suggesting that the molecular dynamics simulation results can be used to obtain information about the specific interactions which contribute to the total free energy of cooperativity. These results provide encouragement to begin a systematic investigation of the molecular basis of the subunit interactions between the ${\alpha}$1 and ${\beta}$2 chains of Hb A by designing appropriate r Hbs. These studies could lead to the design of Hbs with desired cooperativity in the oxygenation process and to the restoration of functional properties of abnormal hemoglobins associated with hemoglobinopathies. Thus, the present results also have the implications in using gene therapy to treat patients with hemoglobinpathies.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2005.09a
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• pp.313-318
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• 2005

Estimating the reliability of protein-protein interaction data sets obtained by high-throughput technologies such as yeast two-hybrid assays and mass spectrometry is of great importance. We develop a maximum likelihood estimation method that uses both protein localization and gene expression data to estimate the reliability of protein interaction data sets. By integrating protein localization data and gene expression data, we can obtain more accurate estimates of the reliability of various interaction data sets. We apply the method to protein physical interaction data sets and protein complex data sets. The reliability of the yeast two-hybrid interactions by Ito et al. (2001) is 27%, and that by Uetz et at.(2000) is 68%. The reliability of the protein complex data sets using tandem affinity purification-mass spec-trometry (TAP) by Gavin et at. (2002) is 45%, and that using high-throughput mass spectrometric protein complex identification (HMS-PCI) by Ho et al. (2002) is 20%. The method is general and can be applied to analyze any protein interaction data sets.

• Reproductive and Developmental Biology
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• v.34 no.1
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• pp.7-13
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• 2010

The binding affinity constants ($p(Od)_{50}$) and molecular docking scores (OS) between porcine odorant binding proteins pOBP (1HQP) and pPBP (1GM6) as receptor and a series of tetrahydrofuran-2-yl (A & B) analogues as substrate, and their interactions were discussed quantitatively using three-dimensional quantitative structure-activity relationship (30-QSAR) models. The statistical qualities of the optimized CoMF A models for pOBP were better than those of the CoMSIA models. The binding affinity constants and OS between substrate and receptor molecules were dependent upon steric and hydrophobic interaction. The DS constants of the substrates into the binding site of OBP (1HQP) were bigger than those of PBP (1GM6). The resulting contour maps produced by the optimized CoMFA model were used to identify the structural features relevant to the binding affinity in binding site of pOBP.

• Molecules and Cells
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• v.37 no.7
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• pp.518-525
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• 2014

Gammaherpesvirus (${\gamma}HV$) infection of the central nervous system (CNS) has been implicated in diverse neurological diseases, and murine ${\gamma}HV$-68 (MHV-68) is known to persist in the brain after cerebral infection. The underlying molecular mechanisms of persistency of virus in the brain are poorly understood. Here, we characterized a unique pattern of MHV-68 persistent infection in neuroblastoma cells. On infection with MHV-68, both murine and human neuroblastoma cells expressed viral lytic proteins and produced virions. However, the infected cells survived productive infection and could be cultured for multiple passages without affecting their cellular growth. Latent infection as well as productive replication was established in these prolonged cultures, and lytic replication was further increased by treatment with lytic inducers. Our results provide a novel system to study persistent infection of ${\gamma}HVs$ in vitro following de novo infection and suggest application of MHV-68 as a potential gene transfer vector to the brain.

• Natural Product Sciences
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• v.24 no.2
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• pp.88-92
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• 2018

The present study was undertaken to investigate the isolated compounds from the stem bark of Garcinia atroviridis as potential cholinesterase inhibitors and the ligand-enzyme interactions of selected bioactive compounds in silico. The in vitro cholinesterase results showed that quercetin (3) was the most active AChE inhibitor ($12.65{\pm}1.57{\mu}g/ml$) while garcinexanthone G (6) was the most active BChE inhibitor ($18.86{\pm}2.41{\mu}g/ml$). It is noteworthy to note that compound 6 was a selective inhibitor with the selectivity index of 11.82. Molecular insight from docking interaction further substantiate that orientation of compound 6 in the catalytic site which enhanced its binding affinity as compared to other xanthones. The nature of protein-ligand interactions of compound 6 is mainly hydrogen bonding, and the hydroxyl group of compound 6 at C-10 is vital in BChE inhibition activity. Therefore, compound 6 is a notable lead for further drug design and development of BChE selective inhibitor.