• Genomics & Informatics
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• 제13권1호
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• pp.15-24
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• 2015

Fatty acid synthase (FASN, EC 2.3.1.85), is a multi-enzyme dimer complex that plays a critical role in lipogenesis. This lipogenic enzyme has gained importance beyond its physiological role due to its implications in several clinical conditions-cancers, obesity, and diabetes. This has made FASN an attractive pharmacological target. Here, we have attempted to predict the theoretical models for the human enoyl reductase (ER) and ${\beta}$-ketoacyl reductase (KR) domains based on the porcine FASN crystal structure, which was the structurally closest template available at the time of this study. Comparative modeling methods were used for studying the structure-function relationships. Different validation studies revealed the predicted structures to be highly plausible. The respective substrates of ER and KR domains-namely, trans-butenoyl and ${\beta}$-ketobutyryl-were computationally docked into active sites using Glide in order to understand the probable binding mode. The molecular dynamics simulations of the apo and holo states of ER and KR showed stable backbone root mean square deviation trajectories with minimal deviation. Ramachandran plot analysis showed 96.0% of residues in the most favorable region for ER and 90.3% for the KR domain, respectively. Thus, the predicted models yielded significant insights into the substrate binding modes of the ER and KR catalytic domains and will aid in identifying novel chemical inhibitors of human FASN that target these domains.

• Molecules and Cells
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• 제27권6호
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• pp.651-656
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• 2009

The formation of ${\beta}$-amyloid peptide ($A{\beta}$) is initiated from cleavage of amyloid precursor protein (APP) by a family of protease, ${\alpha}$-, ${\beta}$-, and ${\gamma}$-secretase. Sub W, a substrate peptide, consists of 10 amino acids, which are adjacent to the ${\beta}$-cleavage site of wild-type APP, and Sub M is Swedish mutant with double mutations on the left side of the ${\beta}$-cleavage site of APP. Sub W is a normal product of the metabolism of APP in the secretary pathway. Sub M is known to increase the efficiency of ${\beta}$-secretase activity, resulting in a more specific binding model compared to Sub W. Three-dimensional structures of Sub W and Sub M were studied by CD and NMR spectroscopy in water solution. On the basis of these structures, interaction models of ${\beta}$-secretase and substrate peptides were determined by molecular dynamics simulation. Four hydrogen bonds and one water-mediated interaction were formed in the docking models. In particular, the hydrogen bonding network of Sub M-BACE formed spread over the broad region of the active site of ${\beta}$-secretase (P5-P3'), and the side chain of P2- Asn formed a hydrogen bond specifically with the side chain of Arg235. These are more favorable to the cleavage of Sub M by ${\beta}$-secretase than Sub W. The two substrate peptides showed different tendency to bind to ${\beta}$-secretase and this information may useful for drug development to treat and prevent Alzheimer's disease.

• 한국생물정보학회:학술대회논문집
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• 한국생물정보시스템생물학회 2005년도 BIOINFO 2005
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• pp.139-143
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• 2005

Cytochrome P450 14${\alpha}$-sterol demethylase enzyme (CYP51) is the target a of azole type antifungals. The azole blocks the ergosterol synthesis and thereby inhibits fungal growth. A three-dimensional (3D) homology model of CYP51 from Candida albicans was constructed based on the X-ray crystal structure of CYP51 from Mycobacterium tuberculosis. Using this model, the binding modes for the substrate (24-methylene-24, 25-dihydrolanosterol) and the known inhibitors (fluconazole, voriconazole, oxiconazole, miconazole) were predicted from docking. Virtual screening was performed employing Structure Based Focusing (SBF). In this procedure, the pharmacophore models for database search were generated from the protein-ligands interactions each other. The initial structure-based virtual screening selected 15 compounds from a commercial available 3D database of approximately 50,000 molecule library, Being evaluated by a cell-based assay, 5 compounds were further identified as the potent inhibitors of Candida albicans CYP51 (CACYP51) with low minimal inhibitory concentration (MIC) range. BMD-09-01${\sim}$BMD-09-04 MIC range was 0.5 ${\mu}$g/ml and BMD-09-05 was 1 ${\mu}$g/ml. These new inhibitors provide a basis for some non-azole antifungal rational design of new, and more efficacious antifungal agents.

• 한국해양공학회지
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• 제21권2호
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• pp.67-74
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• 2007

Maritime and Ocean Engineering Research Institute (MOERI), a branch of KORDI, has designed and manufactured a model of an autonomous underwater vehicle (AUV) named ISiMI (Integrated Submergible for Intelligent Mission Implementation). ISiMI is an AUV platform to satisfy the various needs of experimental test required for development of challenging technologies newly investigated in the field of underwater robot; control and navigational algorithms and software architectures. The main design goal of ISiMI AUV is downsizing which will reduce substantially the operating cost compared to other vehicles previously developed in KORDI such as VORAM or DUSAUV. As a result of design and manufacturing process, ISiMI is implemented to be 1.2 m in length, 0.17 m in diameter and weigh 20 kg in air. A series of tank test is conducted to verify the basic functions of ISiMI in the Ocean Engineering Basin of MOERI, which includes manual control with R/F link, auto depth, auto heading control and a final approach control for underwater docking. This paper describes the implementation of ISiMI system and the experimental results to verify the function of ISiMI as a test-bed AUV platform.

• 한국해양공학회:학술대회논문집
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• 한국해양공학회 2002년도 춘계학술대회 논문집
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• pp.243-250
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• 2002

According to Ocean Korea 21, a basic plan established by the Ministry of Maritime Affairs and Fisheries (MOMAF) of Korea in May 2000, Korea Research Institute of Ships and Ocean Engineering (KRISO) proposed a program for the development of a deep-sea unmanned underwater vehicle (UUV) to explore deep sea for scientific purpose. KRISO has launched a project in May 2001 under the support of MOMAF. The deep-sea unmanned underwater vehicle will be applied to scientific researches in deep-sea as well as in shallow water. For operation of underwater vehicles in shallow water near the Korean Peninsula, a special design is required because of strong tidal current. In addition, MOMAF requires the vehicle to be designed for the purpose of long range survey, a long-term observation, and precise works in a specific area. Thus, KRISO has planned to design the system with the functional combination of both ROV and AUV. This paper presents the design of the deep-sea unmanned underwater vehicle.

• 한국항해항만학회지
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• 제31권8호
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• pp.637-643
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• 2007

많은 분야에서 장비 또는 상용 프로그램이 개발되고 있고, 새로운 기술과 타사 제품의 장점이 더해지면서 점차 복잡해져가고 있는 추세이다. 이러한 점차 복잡해져가는 장비의 사용성(Usability)을 증진시키기 위해 정보를 통합하는 설계(Information Integration Design)가 주목을 받게 되었다. 하지만 정보 통합이 절대적으로 좋은 것일까? 본 논문에서는 각 나라의 선급에서 추진하고 있는 Conning Display 설계에 대한 연구를 통하여, 과도한 정보 통합 보다 정보를 통합하는 과정 속에서 행해지는 정보의 분산(Information Distribution)이 더욱 효율적임을 보이고자 하였다. 이를 위하여, 여러 인간공학적 연구 방법을 적용하여 Conning Display를 설계해 보았으며, 수행도 평가 실험을 실시하였다. 실험 결과 적절한 수의 정보를 적절한 곳에 배치한 대양(연안) 항해 시 그리고 목적 항 입출항시로 구분된 Conning Display가 더욱 효과적인 것을 알 수 있었다.

• 한국산학기술학회논문지
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• 제12권8호
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• pp.3626-3635
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• 2011

모듈러 로봇은 기존 바퀴 혹은 다리를 가지고 있는 이동용 로봇이 가지는 공간 이동의 제한성을 극복하기 위해 개발된 로봇이다. 이는 다리형 로봇의 경우 이동 속도나 지형 등에 있어 균형 잡기 등에 어려움이 존재하며, 바퀴 이동형 로봇의 경우 요철과 둔턱 등을 극복하는데 한계를 지니게 된다. 이에 비해 모듈러 로봇의 경우 형상의 변경이 용이하며 이를 통해 자유로운 이동이 가능하여 이동성능에 제약을 극복할 수 있는 로봇이다. 하지만 모듈러 로봇의 경우 구동메커니즘 뿐만 아니라 형상 변경에 따른 결합 분리 메카니즘에 대한 연구도 진행되어야 한다. 이에 본 논문에서는 네 종류의 모듈러 로봇 결합 메커니즘을 제안하였다. 또한 각 모듈러 로봇 결합 메커니즘에 따른 결합 알고리즘을 제시하였다. 그리고 제안된 구조를 실제 구현하여 구조의 유용성을 검증하였다.

• Biomolecules & Therapeutics
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• 제25권5호
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• pp.535-544
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• 2017

Carnosol is a phenolic antioxidant present in rosemary (Rosmarinus officinalis). It is known for anti-inflammatory effects, analgesic activity and anti-cancer effects. However, no study has been dedicated yet to its effect on atopic dermatitis (AD). Here, we show that carnosol effectively inhibited LPS-induced nitric oxide (NO) generation and expression of inflammatory marker proteins (iNOS and COX-2) in RAW 264.7 cells. In addition, carnosol effectively inhibits the phosphorylation of STAT3 and DNA binding activity in RAW 264.7 cells. Pull down assay and docking model analysis showed that carnosol directly binds to the DNA binding domain (DBD) of STAT3. We next examined the anti-atopic activity of carnosol ($0.05{\mu}g/cm^2$) using 5% Phthalic anhydride (PA)-induced AD model in HR1 mice. Carnosol treatment significantly reduced 5% PA-induced AD like skin inflammation in skin tissues compared with control mice. Moreover, carnosol treatment inhibits the expression of iNOS and COX-2 in skin tissue. In addition, the levels of $TNF-{\alpha}$, $IL-1{\beta}$, and Immunoglobulin-E in blood serum was significantly decreased in carnosol treated mice compared with those of 5% PA treated group. Furthermore, the activation of STAT3 in skin tissue was decreased in carnosol treated mice compared with control mice. In conclusion, these findings suggest that carnosol exhibited a potential anti-AD activity by inhibiting pro-inflammatory mediators through suppression of STAT3 activation via direct binding to DBD of STAT3.

• Journal of Microbiology and Biotechnology
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• 제17권10호
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• pp.1712-1716
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• 2007

To generate new scaffold candidates as highly selective and potent cyelin-dependent kinase (CDK) inhibitors, structure-based drug screening was performed utilizing 3D pharmacophore conformations of known potent inhibitors. As a result, CR229 (6-bromo-2,3,4,9-tetrahydro-carbolin-1-one) was generated as the hit-compound. A computational docking study using the X-ray crystallographic structure of CDK2 in complex with CR229 was evaluated. This predicted binding mode study of CR229 with CDK2 demonstrated that CR229 interacted effectively with the Leu83 and Glu81 residues in the ATP-binding pocket of CDK2 for the possible hydrogen bond formation. Furthermore, biochemical studies on inhibitory effects of CR229 on various kinases in the human cervical cancer HeLa cells demonstrated that CR229 was a potent inhibitor of CDK2 ($IC_{50}:\;3\;{\mu}M$), CDKI ($IC_{50}:\;4.9\;{\mu}M$), and CDK4 ($IC_{50}:\;3\;{\mu}M$), yet had much less inhibitory effect ($IC_{50}:>20\;{\mu}M$) on other kinases, such as casein kinase 2-${\alpha}1$ (CK2-${\alpha}1$), protein kinase A (PKA), and protein kinase C (PKC). Accordingly, these data demonstrate that CR229 is a potent CDK inhibitor with anticancer efficacy.

• Journal of Microbiology and Biotechnology
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• 제28권5호
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• pp.671-678
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• 2018

Papiliocin, isolated from the swallowtail butterfly (Papilio xuthus), is an antimicrobial peptide with high selectivity against gram-negative bacteria. We previously showed that the N-terminal helix of papiliocin (PapN) plays a key role in the antibacterial and anti-inflammatory activity of papiliocin. In this study, we measured the selectivity of PapN against multidrug-resistant gram-negative bacteria, as well as its anti-inflammatory activity. Interactions between Trp2 of PapN and lipopolysaccharide (LPS), which is a major component of the outer membrane of gram-negative bacteria, were studied using the Trp fluorescence blue shift and quenching in LPS micelles. Furthermore, using circular dichroism, we investigated the interactions between PapN and LPS, showing that LPS plays critical roles in peptide folding. Our results demonstrated that Trp2 in PapN was buried deep in the negatively charged LPS, and Trp2 induced the ${\alpha}$-helical structure of PapN. Importantly, docking studies determined that predominant electrostatic interactions of positively charged arginine residues in PapN with phosphate head groups of LPS were key factors for binding. Similarly, hydrophobic interactions by aromatic residues of PapN with fatty acid chains in LPS were also significant for binding. These results may facilitate the development of peptide antibiotics with anti-inflammatory activity.