• Bulletin of the Korean Chemical Society
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• 제34권9호
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• pp.2680-2684
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• 2013

Protein kinases (PKs) are an important source of drug targets, especially in oncology. With 500 or more kinases in the human genome and only few kinase inhibitors approved, kinase inhibitor discovery is becoming more and more valuable. Because the discovery of kinase inhibitors with an increased selectivity is an important therapeutic concept, many researchers have been trying to address this issue with various methodologies. Although many attempts to predict the activity and selectivity of kinase inhibitors have been made, the issue of selectivity has not yet been resolved. Here, we studied kinase selectivity by generating predictive models and analyzing their descriptors by using kinase-profiling data. The 5-fold cross-validation accuracies for the 51 models were between 72.4% and 93.7% and the ROC values for all the 51 models were over 0.7. The phylogenetic tree based on the descriptor distance is quite different from that generated on the basis of sequence alignment.

• BMB Reports
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• 제28권3호
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• pp.191-196
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• 1995

The role of polyamines in skeletal myoblast differentiation was investigated using the polyamine metabolic inhibitor methylglyoxal bis(guanylhydrazone)(MGBG). Concentrations of intracellular free spermidine and spermine increased 2 to 2.5-fold at the onset of myoblast fusion. The systhesis of actin, and creatine kinase activity both dramatically increased during myotube formation. However, MGBG at a concentration of 0.5 mM not only abolished the increase of intracellular free polyamines, but also reduced cell fusion to almost half the level of untreated cells, without noticeable morphological alteration. The production of actin, and creatine kinase activity were almost completely abolished by MGBG. The inhibition of myoblast fusion by MGBG was partially recovered with 0.1 mM of spermidine or spermine added externally. Results indicate that polyamines are necessary for normal myoblast differentiation. Since the first indication of myoblast differentiation is alignment of muscle cells and membrane fusion of adjacent cells, and since polyamine depletion completely inhibited the synthesis of actin, which might be associted with membranes, polyamine might be involved in myoblast differentiation through membrane reorganization events.

• 통합자연과학논문집
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• 제8권4호
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• pp.273-284
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• 2015

Chemoattractant Receptor Homologous molecule expressed on Th2 cells (CRTh2) is a chemoattractant receptor with seven transmembrane helices targeted for inflammatory diseases such as asthma and allergic rhinitis. In this study, pharmacophore based Comparative Molecular Similarity Indices Analysis (CoMSIA) were performed on the series of 2-(2-(benzylthio)-1H-benzo[d]imidazol-1-yl) acetic acids derivatives. Initially, GASP module was used for generation of pharmacophore models using five highly active compounds from the dataset. Among the generated pharmacophores, the best pharmacophore model was selected based on fitness score and was used as template for the alignment of compounds which was used for CoMSIA analysis. The best predictions were obtained utilizing steric, hydrophobic and H-bond acceptor parameters showing a $q^2$=0.559 and $r^2$=0.730. 15 test set compounds was used to investigate the predictive ability of the CoMSIA model. Contour maps suggested that presence of bulky substituents and H-bond acceptor atoms at $5^{th}$ position of benzene ring will increase the activity of the compounds. The results obtained from this study will be useful to design more potent CRTh2 antagonists.

• 한국CDE학회논문집
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• 제14권6호
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• pp.404-414
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• 2009

In the computational molecular analysis, 3D structural comparison for protein searching plays a very important role. As protein databases have been grown rapidly in size, exhaustive search methods cannot provide satisfactory performance. Because exhaustive search methods try to handle the structure of protein by using sphere set which is converted from atoms set, the similarity calculation about two sphere sets is very expensive. Instead, the filter-and-refine paradigm offers an efficient alternative to database search without compromising the accuracy of the answers. In recent, a very fast algorithm based on the inter-atomic distance has been suggested by Ballester and Richard. Since they adopted the moments of distribution with inter-atomic distance between atoms which are rotational invariant, they can eliminate the structure alignment and orientation fix process and perform the searching faster than previous methods. In this paper, we propose a new 3D shape descriptor. It has properties of the general shape distribution and useful property in screening the molecular database. We show some experimental results for the validity of our method.

• Bulletin of the Korean Chemical Society
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• 제26권6호
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• pp.952-958
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• 2005

Angiotensin-converting enzyme (ACE) is known to be primarily responsible for hypertension. Threedimensional quantitative structure-activity relationship (3D-QSAR) models have been constructed using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) for a series of 28 ACE inhibitors. The availability of ACE crystal structure (1UZF) provided the plausible biological orientation of inhibitors to ACE active site (C-domain). Alignment for CoMFA obtained by docking ligands to 1UZF protein using FlexX program showed better statistical model as compared to superposition of corresponding atoms. The statistical parameters indicate reasonable models for both CoMFA ($q^2$ = 0.530, $r^2$ = 0.998) and CoMSIA ($q^2$ = 0.518, $r^2$ = 0.990). The 3D-QSAR analyses provide valuable information for the design of ACE inhibitors with potent activity towards C-domain of ACE. The group substitutions involving the phenyl ring and carbon chain at the propionyl and sulfonyl moieties of captopril are essential for better activity against ACE.

• 폴리머
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• 제32권3호
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• pp.290-294
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• 2008

러빙한 고분자 필름이 액정 분자와 증착된 분자의 배향을 유도하는 메커니즘을 이해하고자 $\pi$ 전자들의 공액구조가 주사슬과 곁사슬에 각각 있는 polyimide와 polyyinylcinnamate를 사용하여 필름과 LC 셀을 만들어 편광 UV/Vis 분광실험으로 조사하였다. 러빙한 필름 내에 형성되는 이방성, LC 셀의 액정 방향자, 그리고 종착된 pentacene의 배열방향을 측정하여, 액정배향은 microgroove 영향보다는 분자간 상호작용에 의하여 우선적으로 유도되는 반면에 pentacene 증착의 경우에는 러빙에 의하여 형성된 필름 표면의 microgroove 영향으로 배향이 유도되는 것을 알 수 있었다.

• Journal of Microbiology and Biotechnology
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• 제20권9호
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• pp.1283-1287
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• 2010

In eukaryotes, eRF3 participates in translation termination and belongs to the superfamily of GTPases. In this work, the dissociation constants for nucleosides bound to Euplotes octocarinatus eRF3 in the presence and absence of eRF1a were determined using fluorescence spectra methods. Furthermore, a GTP hydrolyzing assay of eRF3 was carried out using an HPLC method, and the kinetic parameters for GTP hydrolysis by eRF3 were determined. Consistent with data from humans, the results showed that eRF1a promoted the binding of GTP to eRF3 and the GTP hydrolyzing activity of eRF3. However, in contrast to the lack of GTP binding in the absence of eRF1 in human eRF3, the E. octocarinatus eRF3 was able to bind GTP by itself. The nucleotide binding affinity of the E. octocarinatus eRF3 also differed from the human data. A structure model and amino acid sequence alignment of potential G domains indicated that these differences may be due to valine 317 and glutamate 452 displacing the conserved glycine and lysine involved in GTP binding.

• 폴리머
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• 제26권4호
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• pp.431-438
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• 2002

편광 푸리에 변환 적외선 분광법을 이용하여 액정 디스플레이의 배향막으로 널리 사용되는 폴리이미드 필름의 편광 자외선 조사에 따른 액정의 배향성과 열적 안정성을 연구하였다. 편광자외선이 조사된 폴리이미드의 경우, 조사된 편광자외선의 극성 방향에 평행한 폴리이미드 분자들의 우선적인 광분해 반응으로 인하여 편광자외선 조사 후 남아 있는 폴리이미드 분자들은 조사된 편광자외선 극성 방향과 수직 배향을 나타내었다. 하지만 러빙 처리된 폴리이미드 필름은 러빙 방향과 평행하게 폴리이미드 분자들의 재배향이 유도됨을 확인하였다. 또한 편광자외선이 조사된 폴리이미드 배향막이 편광자외선 조사를 통한 폴리이미드 분자들의 단편화 반응 때문에 러빙 처리된 폴리이미드 배향막 보다는 열적 안정성이 저하됨을 확인하였다.

• 천문학회보
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• 제46권2호
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• pp.38.1-38.1
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• 2021

Dust polarization depends on the physical and mechanical properties of dust, as well as the properties of local environments. To understand how dust polarization varies with grain mechanical properties and the local environment, in this paper, we model the wavelength-dependence polarization of starlight and polarized dust emission by aligned grains by simultaneously taking into account grain alignment and rotational disruption by radiative torques (RATs). We explore a wide range of the local radiation field and grain mechanical properties characterized by tensile strength. We find that the maximum polarization and the peak wavelength shift to shorter wavelengths as the radiation strength U increases due to the enhanced alignment of small grains. Grain rotational disruption by RATs tends to decrease the optical-near infrared polarization but increases the ultraviolet polarization of starlight due to the conversion of large grains into smaller ones. In particular, we find that the submillimeter (submm) polarization degree at 850㎛(P850) does not increase monotonically with the radiation strength or grain temperature (Td), but it depends on the tensile strength of grain materials. Our physical model of dust polarization can be tested with observations toward star-forming regions or molecular clouds irradiated by a nearby star, which have higher radiation intensity than the average interstellar radiation field. Finally, we compare our predictions of the P850-Td relationship with Planck data and find that the observed decrease of P850 with Td can be explained when grain disruption by RATs is accounted for, suggesting that interstellar grains unlikely to have a compact structure but perhaps a composite one. The variation of the submm polarization with U (or Td)can provide a valuable constraint on the internal structures of cosmic dust

• 생약학회지
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• 제52권2호
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• pp.69-76
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• 2021

Cannabis sativa is an important industrial plant utilized to produce fiber, oil, and medicinal ingredients. A chemotype of cannabis is divided into "Drug type" with predominance of tetrahydrocannabinolic acid (THCA) and "Fiber type" with cannabidiolic acid (CBDA). To develop molecular markers for the discrimination of these two types, nucleotide sequences of THCA synthase and CBDA synthase as well as their pseudogenes were retrieved from the recently published cannabis genome in chromosome scale. Gene-specific SNPs were discovered by multiple alignment of these sequences, and 2 dominant marker sets from each gene were designed for selective amplification. Our markers successfully identified "Drug type" and "Fiber type" cannabis plants as well as forensic samples including processed materials. Our molecular markers will provide a fast and efficient system for molecular-based identification of the cannabis plant.