• Bulletin of the Korean Chemical Society
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• 제33권3호
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• pp.911-916
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• 2012

Ion selectivity in a simple cyclic peptide nanotube, composed of four cyclo[-(D-Ala-Glu-D-Ala-Gln)$_2-$] units, is investigated by calculating the PMF profiles of $Na^+$, $K^+$, and $Cl^-$ ions permeating through the peptide nanotube in water. The final PMF profiles of the ions obtained from the umbrella sampling (US) method show an excellent agreement with those from the thermodynamic integration (TI) method. The PMF profiles of $Na^+$ and $K^+$ display free energy wells while the PMF curve of $Cl^-$ features free energy barriers, indicating the selectivity of the cyclic peptide nanotube to cations. Decomposition of the total mean force into the contribution from each component in the system is also accomplished by using the TI method. The mean force decomposition profiles of $Na^+$ and $K^+$ demonstrate that the dehydration free energy barriers by water molecules near the channel entrance and inside the channel are completely compensated for by attractive electrostatic interactions between the cations and carbonyl oxygens in the nanotube. In the case of $Cl^-$, the dehydration free energy barriers are not eliminated by an interaction between the anion and the peptide nanotube, leading to the high free energy barriers in the PMF profile. Calculations of the coordination numbers of the ions with oxygen atoms pertaining to either water molecules or carbonyl groups in the peptide nanotube reveal that the stabilization of the cations in the midplane regions of the nanotube arises from the favorable interaction of the cations with the negatively charged carbonyl oxygens.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3735-3742
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• 2013

Background: Cardamom (Elettaria cardamom), also known as "Queen of Spices", has been traditionally used as a culinary ingredient due to its pleasant aroma and taste. In addition to this role, studies on cardamom have demonstrated cancer chemopreventive potential in in vitro and in vivo systems. Nevertheless, the precise poly-pharmacological nature of naturally occurring chemo-preventive compounds in cardamom has still not been fully demystified. Methods:In this study, an effort has been made to identify the proapoptopic, anti-inflammatory, anti-proliferative, anti-invasive and anti-angiogenic targets of Cardamom's bioactive principles (eucalyptol, alpha-pinene, beta-pinene, d-limonene and geraniol) by employing a dual reverse virtual screening protocol. Experimentally proven target information of the bioactive principles was annotated from bioassay databases and compared with the virtually screened set of targets to evaluate the reliability of the computational identification. To study the molecular interaction pattern of the anti-tumor action, molecular docking simulation was performed with Auto Dock Pyrx. Interaction studies of binding pose of eucalyptol with Caspase 3 were conducted to obtain an insight into the interacting amino acids and their inter-molecular bondings. Results:A prioritized list of target proteins associated with multiple forms of cancer and ranked by their Fit Score (Pharm Mapper) and descending 3D score (Reverse Screen 3D) were obtained from the two independent inverse screening platforms. Molecular docking studies exploring the bioactive principle targeted action revealed that H- bonds and electrostatic interactions forms the chief contributing factor in inter-molecular interactions associated with anti-tumor activity. Eucalyptol binds to the Caspase 3 with a specific framework that is well-suited for nucleophilic attacks by polar residues inside the Caspase 3 catalytic site. Conclusion:This study revealed vital information about the poly-pharmacological anti-tumor mode-of-action of essential oils in cardamom. In addition, a probabilistic set of anti-tumor targets for cardamom was generated, which can be further confirmed by in vivo and in vitro experiments.

• 정보과학회 컴퓨팅의 실제 논문지
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• 제20권12호
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• pp.700-705
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• 2014

애너그램은 주어진 문자들을 재배열하여 숨겨진 단어를 찾아내는 철자바꾸기 놀이로, 문제를 빨리 풀어내는 사람들은 제약 만족 네트워크의 병렬적 탐색에 의해 문제를 해결한다. 본 연구에서는 이러한 인지적 현상을 모델링한 분자 애너그램 풀이 알고리즘을 제시하였다. 문자를 DNA 서열로 인코딩하고, 문자 DNA 가닥을 연결하여 바이그램과 단어 서열을 만들었다. DNA 혼성화, 연결, 젤 전기영동, 추출 연산을 수행해 문자와 바이그램 집합으로부터 답을 찾는 데 필요한 바이그램을 추출한 후, 추출한 바이그램과 단어 집합으로부터 다시 네 가지 DNA 연산을 반복하여 답을 찾는다. 분자 실험 결과 분자 컴퓨터는 정답인 단어와 오답인 단어를 구분해낼 수 있었다. 이를 통해 인간의 병렬적 사고과정을 분자 컴퓨터로 모델링할 수 있는 가능성을 보였다.

• 대한기계학회논문집A
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• 제41권7호
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• pp.621-627
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• 2017

다양한 신경성 퇴행 질병을 유발하는 아밀로이드 섬유의 기계적 특징에 대한 이해는 아밀로이드 성장 메커니즘에 직접 관련되어 있기 때문에 질병 역학적 관점에서 많은 연구 진행 되어 왔다. 최근 아밀로이드 섬유의 높은 물성 값과 자가 결합능력을 통해 새로운 재료로 이용 하려는 시도가 진행되고 있다. 본 연구에서는 심혈관 질환을 유발하는 transthyretin($TTR_{105-115}$)의 핵심 영역의 기계적 특성을 분자 동역학 전산 역학을 통해 평가했다. 특히 end-terminal capping의 효과가 $TTR_{105-115}$의 구조적 안정성에 미치는 영향을 평가했다. 인장모사 분자 동역학을 통해(steered molecular dynamics, SMD) 기계적 거동과 물성을 측정하였다. 재료의 기계적 특성에 영향을 주는 인자를 밝히고 자연 모사 재료로써의 활용 가능성에 대한 제시를 하였다.

• Genomics & Informatics
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• 제21권3호
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• pp.32.1-32.11
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• 2023

Resistance to anti-tuberculosis drugs, especially ethambutol (EMB), has been widely reported worldwide. EMB resistance is caused by mutations in the embB gene, which encodes the arabinosyl transferase enzyme. This study aimed to detect mutations in the embB gene of Mycobacterium tuberculosis from Papua and to evaluate their impact on the effectiveness of EMB. We analyzed 20 samples of M. tuberculosis culture that had undergone whole-genome sequencing, of which 19 samples were of sufficient quality for further bioinformatics analysis. Mutation analysis was performed using TBProfiler, which identified M306L, M306V, D1024N, and E378A mutations. In sample TB035, the M306L mutation was present along with E378A. The binding affinity of EMB to arabinosyl transferase was calculated using AutoDock Vina. The molecular docking results revealed that all mutants demonstrated an increased binding affinity to EMB compared to the native protein (-0.948 kcal/mol). The presence of the M306L mutation, when coexisting with E378A, resulted in a slight increase in binding affinity compared to the M306L mutation alone. The molecular dynamics simulation results indicated that the M306L, M306L + E378A, M306V, and E378A mutants decreased protein stability. Conversely, the D1024N mutant exhibited stability comparable to the native protein. In conclusion, this study suggests that the M306L, M306L + E378A, M306V, and E378A mutations may contribute to EMB resistance, while the D1024N mutation may be consistent with continued susceptibility to EMB.

• Bulletin of the Korean Chemical Society
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• 제31권3호
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• pp.606-610
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• 2010

Aminoacyl-tRNA synthetases (aaRSs) play vital roles in protein biosynthesis of living organisms and are interesting antibacterial drug targets. In order to find out new inhibitor candidate molecules as antibacterial agent, the binding modes of the candidate molecules were investigated at the active sites of aaRSs by molecular docking study. The docking simulations were performed with 48 compounds from four different scaffolds into the eight different aaRSs. The results show that scaffolds 3 and 4 compounds have consistently better binding capabilities, specifically for HisRS (E. coli) and IleRS (S. aureus). The binding modes of the best compounds with the proteins were well compatible with those of two ligands in crystal structures. Therefore, we expect that the final compounds we present may have reasonable aaRS inhibitory activity.

• Bulletin of the Korean Chemical Society
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• 제32권11호
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• pp.4027-4034
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• 2011

$CaCO_3$ crystalline structures having novel assemblies were in situ fabricated as analogs of naturally occurring proteins and polysaccharides for biomineralization. The calcite crystal was mineralized in a poly(vinyl alcohol)-$Ca^{2+}$ complex film immersed in a $Na_2CO_3$ solution containing poly(aspartic acid). The morphology and size of the $CaCO_3$ crystals were tuned by varying the concentration of poly(aspartic acid). The mechanisms of their nucleation orientation and formation were investigated experimentally and through molecular dynamics (MD) simulations in order to obtain a better understanding of the interactions between the polymers and the crystal at the molecular level. Both the MD results and experimental results indicate that the interaction between PVA and calcite mainly depends on the concentration of the polymer. The novel approach proposed herein for the fabrication of inorganic crystalline assembly structures can be used to fabricate precise crystalline structures.

• Bulletin of the Korean Chemical Society
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• 제33권3호
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• pp.862-868
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• 2012

Based on the recently derived general expression for the rates of diffusion-controlled reactions, we calculate the rates of dismutation of the superoxide anion radical catalyzed by Cu/Zn superoxide dismutases (SOD). This is the first attempt to calculate the absolute rates of diffusion-controlled enzyme reactions based on the atomiclevel molecular dynamics simulations. All solvent molecules are included explicitly and the effects of the structural flexibility of enzyme, especially those of side chain motions near the active site, are included in the present calculation. In addition, the actual mobility of the substrate molecule is taken into account, which may change as the molecule approaches the active site of enzyme from the bulk solution. The absolute value of the rate constant for the wild type SOD reaction obtained from MD simulation is shown to be in good agreement with the experimental value. The calculated reactivity of a mutant SOD is also in agreement with the experimental result.

• 설비공학논문집
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• 제30권1호
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• pp.33-43
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• 2018

This study numerically investigated statistic and dynamic behaviors of the water droplet on plate with or without various structured-pillars at nano-scale by molecular dynamics simulation. This study considered smooth plate, plate with the rectangular-structured pillar, and the plate with dual-structured pillar under various characteristic energy conditions. The static behavior of water droplet depending on the plate shape, plate surface energy, and the pillar characteristics were examined. After the water droplet reaches its steady state, this study investigated the dynamic behavior of the water droplet by applying a constant force. Finally, this study investigated the static and dynamic behaviors of the water droplet by measuring its contact angle and contact angle hysteresis. As a result, we found that the structure was more hydrophobic.

• Genomics & Informatics
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• 제15권4호
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• pp.142-146
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• 2017

More effective production of human insulin is important, because insulin is the main medication that is used to treat multiple types of diabetes and because many people are suffering from diabetes. The current system of insulin production is based on recombinant DNA technology, and the expression vector is composed of a preproinsulin sequence that is a fused form of an artificial leader peptide and the native proinsulin. It has been reported that the sequence of the leader peptide affects the production of insulin. To analyze how the leader peptide affects the maturation of insulin structurally, we adapted several in silico simulations using 13 artificial proinsulin sequences. Three-dimensional structures of models were predicted and compared. Although their sequences had few differences, the predicted structures were somewhat different. The structures were refined by molecular dynamics simulation, and the energy of each model was estimated. Then, protein-protein docking between the models and trypsin was carried out to compare how efficiently the protease could access the cleavage sites of the proinsulin models. The results showed some concordance with experimental results that have been reported; so, we expect our analysis will be used to predict the optimized sequence of artificial proinsulin for more effective production.