• 한국자기공명학회논문지
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• 제17권1호
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• pp.11-18
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• 2013

Rapid advances of computational power and method have made it practical to apply the time-consuming calculations with all-atom force fields and sophisticated potential energies into refining NMR structure. Added to the all-atom force field, generalized-Born implicit solvent model (GBIS) contributes substantially to improving the qualities of the resulting NMR structures. GBIS approximates the effects that explicit solvents bring about even with fairly reduced computational times. Although GBIS is employed in the final stage of NMR structure calculation with experimental restraints, the effects by GBIS on structures have been reported notable. However, the detailed effect is little studied in a quantitative way. In this study, we report GBIS refinements of ubiquitin and GB1 structures by six GBIS models of AMBER package with experimental distance and backbone torsion angle restraints. Of GBIS models tested, the calculations with igb=7 option generated the closest structures to those determined by X-ray both in ubiquitin and GB1 from the viewpoints of root-mean-square deviations. Those with igb=5 yielded the second best results. Our data suggest that the degrees of improvements vary under different GBIS models and the proper selection of GBIS model can lead to better results.

• Bulletin of the Korean Chemical Society
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• 제30권5호
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• pp.1139-1142
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• 2009

Refinement of NMR structures by molecular dynamics (MD) simulations with a solvent model has improved the structural quality. In this study, we applied MD refinement with the generalized Born (GB) implicit solvent model to protein structure determined under membrane-like environments. Despite popularity of the GB model, its applications to the refinement of NMR structures of hydrophobic proteins, in which detergents or organic solvents enclose proteins, are limited, and there is little information on the use of another GB parameter for these cases. We carried out MD refinement of crambin NMR structure in dodecylphosphocholine (DPC) micelles (Ahn et al., J. Am. Chem. Soc. 2006, 128, 4398-4404) with GB/Surface area model and two different surface tension coefficients, one for aquatic and the other for hydrophobic conditions. Our data show that, of two structures by MD refinement with GB model, the one refined with the parameter to consider hydrophobic condition had the better qualities in terms of precision and solvent accessibility.

• 대한화학회지
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• 제57권5호
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• pp.554-559
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• 2013

본 연구에서는 ${\beta}$-D-glucopyranose 분자의 hydroxymethyl group의 두 torsion angle의 변화에 따른 포텐셜 에너지의 변화를 진공 상태와 implicit water 상태에서 연구하였으며 이를 통해 Solvation Energy가 구조에 미치는 영향에 대해서 알아보았다. 계산에 사용한 프로그램은 AMBER package였으며, force field는 GLYCAM_06을 사용하였다. Solvation model은 Hawkins, Cramer, Truhlar 등이 제안한 generalized Born model을 사용하였다. 계산 결과, methyl hydroxyl group 내의 hydroxyl group이 고리구조의 hydroxyl group과 강한 수소결합이 가능한 영역에서 많은 변화가 일어났다. 이를 통해 solvation effect로 인해서 수소 결합의 중요성이 감소했다는 결론을 내렸다.

• Bulletin of the Korean Chemical Society
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• 제35권7호
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• pp.1944-1950
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• 2014

Employment of a time consuming, sophisticated calculation using the all-atom force field and generalized-Born implicit solvent model (GBIS) for refinement of NMR structures has become practical through advances in computational methods and capacities. GBIS refinement improves the qualities of the resulting NMR structures with reduced computational times. However, the contribution of GBIS to NMR structures has not been sufficiently studied in a quantitative way. In this paper, we report the effects of GBIS on the refined NMR structures of ubiquitin (UBQ) and GB1 with subsets of distance restraints derived from experimental data. Random omission prepared a series of distance restraints 0.05, 0.1, 0.3, 0.5, and 0.7 times smaller. For each number, we produced five different restraints for statistical analysis. We then recalculated the NMR structures using CYANA software, followed by GBIS refinements using the AMBER package. GBIS improved both the precision and accuracy of all the structures, but to varied levels. The degrees of improvement were significant when the input restraints were insufficient. In particular, GBIS enabled GB1 to form an accurate structure even with distance restraints of 5%, revealing that the root-mean-square deviation was less than 1 ${\AA}$ from the X-ray backbone structure. We also showed that the efficiency of searching the conformational space was more important for finding accurate structures with the calculation of UBQ with 5% distance restraints than the number of conformations generated. Our data will provide a meaningful guideline to judge and compare the structural improvements by GBIS.

• 한국자기공명학회논문지
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• 제18권1호
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• pp.24-29
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• 2014

Atomistic molecular dynamics (MD) simulation has become mature enabling close approximation of the real behaviors of biomolecules. In biomolecular NMR field, atomistic MD simulation coupled with generalized implicit solvent model (GBIS) has contributed to improving the qualities of NMR structures in the refinement stage with experimental restraints. Here all-atom force fields play important roles in defining the optimal positions between atoms and angles, resulting in more precise and accurate structures. Despite successful applications in refining NMR structure, however, the research that has studied the influence of force fields in GBIS is limited. In this study, we compared the qualities of NMR structures of two model proteins, ubiquitin and GB1, under a series of AMBER force fields-ff99SB, ff99SB-ILDN, ff99SB-NMR, ff12SB, and ff13-with experimental restraints. The root mean square deviations of backbone atoms and packing scores that reflect the apparent structural qualities were almost indistinguishable except ff13. Qualitative comparison of parameters, however, indicates that ff99SB-ILDN is more recommendable, at least in the cases of ubiquitin and GB1.

• Bulletin of the Korean Chemical Society
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• 제30권12호
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• pp.3006-3010
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• 2009

We have performed long time REMD simulation on 15-19 residues of human calcitonin hormone (DFNKF) which is known to form highly ordered amyloid fibril. The simulation started from randomly oriented multiple DFNKF strand. Using all-atom level simulations with the generalized Born solvation (GB) model (param99MOD3), we observed spontaneous formation of ${\beta}$-sheet for tetramer. Interestingly, the current simulation gives anti-parallel sheet as a major conformation, consistent with experiments. The major interaction stabilizing the anti-parallel sheet seems to be the inter-strand hydrogen bond.

• 한국인구학
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• 제29권2호
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• pp.53-88
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• 2006

본 연구의 목적은 장래인구추계를 위하여 논리적이고 상대적으로 정확한 연령별 출산율의 가정치를 설정하는 것이다. 먼저 코호트별 출산순위별 연령별 출산율의 추정과 추계를 위하여 Coale-McNeil 모형을 일반화한 로그감마분포모형을 선택한다. 다음은 보정형의 연령별 출산율 모형을 재생산을 완료하지 않은 상대적으로 젊은 출생코호트를 포함하는 실적치 자료에 맞추기 위하여, 출산력 파라메터를 추정하는 방법을 설명한다. 본 연구는 일련의 출생코호트의 출생순위별 연령별 출산율을 역출하여, 장래의 특정연도 대하여 연령별 출산율을 추계한다. 가령, 2010년의 20세의 연령별 출산율은 1990년에 태어난 출생코호트의 20세에서의 연령별 출산율이고, 2010년의 21세의 연령별 출산율은 1989년에 태어난 출생코호트의 21세에서의 연령별 출산율에 해당한다. 결국 2010년에 태어난 코호트까지의 연령별 출산율의 추계치를 얻게 되면, 2055년도 까지의 기간별(연도별_령별 출산율에 대한 가정치를 설정할 수 있다. 본 연구의 출산력 가정치와 통계청의 2005년 장래인구 특별추계의 가정치 사이에 차이가 나는 것은 털 연구의 출산예측모형에서 혼인연령의 상승과 독신여성의 증가로 인한 출산력 저하의 최근 추세를 제대로 반영하였기 때문이라고 할 수 있으며, 이러한 점에서 본 연구의 출산력 가정치가 논리적이고 합리적이라고 주장할 수 있을 것이다. 그러나 장래인구추계와 관련하여, 출산력 가정치 설정을 위한 출산예측모형의 본질적 과제는 어떻게 기간효과(를 슬기롭게 다루느냐 하는 것이다. 코호트모형을 근간으로 하여, 최근의 실적치를 바탕으로 약간의 기간적 수정을 하는 것을 제외하고는 기간효과를 별도로 취급하기는 쉽지 않다.

• 한국자기공명학회논문지
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• 제19권1호
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• pp.1-10
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• 2015

Refinements with atomistic molecular dynamics (MD) simulation have contributed to improving the qualities of NMR structures. In most cases, the calculations with atomistic MD simulation for NMR structures employ generalized-Born implicit solvent model (GBIS) to take into accounts solvation effects. Developments in algorithms and computational capacities have ameliorated GBIS to approximate solvation effects that explicit solvents bring about. However, the quantitative comparison of NMR structures in the latest GBIS and explicit solvents is lacking. In this study, we report the direct comparison of NMR structures that atomistic MD simulation coupled with GBIS and water molecules refined. Two model proteins, GB1 and ubiquitin, were recalculated with experimental distance and torsion angle restraints, under a series of simulated annealing time steps. Whereas the root mean square deviations of the resulting structures were apparently similar, AMBER energies, the most favored regions in Ramachandran plot, and MolProbity clash scores witnessed that GBIS-refined structures had the better geometries. The outperformance by GBIS was distinct in the structure calculations with sparse experimental restraints. We show that the superiority stemmed, at least in parts, from the inclusion of all the pairs of non-bonded interactions. The shorter computational times with GBIS than those for explicit solvents makes GBIS a powerful method for improving structural qualities particularly under the conditions that experimental restraints are insufficient. We also propose a method to separate the native-like folds from non-violating diverged structures.

• 한국자기공명학회논문지
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• 제26권1호
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• pp.1-9
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• 2022

There are two distinct approaches to improving the quality of protein NMR structures during refinement: all-atom force fields and accumulated knowledge-assisted methods that include Rosetta. Mao et al. reported that, for 40 proteins, Rosetta increased the accuracies of their NMR-determined structures with respect to the X-ray crystal structures (Mao et al., J. Am. Chem. Soc. 136, 1893 (2014)). In this study, we calculated 32 structures of those studied by Mao et al. using all-atom force field and implicit solvent model, and we compared the results with those obtained from Rosetta. For a single protein, using only the experimental NOE-derived distances and backbone torsion angle restraints, 20 of the lowest energy structures were extracted as an ensemble from 100 generated structures. Restrained simulated annealing by molecular dynamics simulation searched conformational spaces with a total time step of 1-ns. The use of GPU-accelerated AMBER code allowed the calculations to be completed in hours using a single GPU computer-even for proteins larger than 20 kDa. Remarkably, statistical analyses indicated that the structures determined in this way showed overall higher accuracies to their X-ray structures compared to those refined by Rosetta (p-value < 0.01). Our data demonstrate the capability of sophisticated atomistic force fields in refining NMR structures, particularly when they are coupled with the latest GPU-based calculations. The straightforwardness of the protocol allows its use to be extended to all NMR structures.

• 대한소아신경학회지
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• 제26권4호
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• pp.227-232
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• 2018

목적: 열성 경련은 생후 6개월부터 만 5세 사이 발생하는 가장 흔한 유형의 경련으로 직계 가족에서 가족력이 존재할 때 더 발생률이 높다. 열성 경련의 발생률과 외부 환경과의 영향에 대하여 아직 정확히 알려진 바가 없다. 본 연구는 열성 경련의 발생과 날씨의 연관성을 파악하기 위해 시행되었다. 방법: 본 연구는 건강보험심사평가원 자료를 바탕으로 진행되었다. 2009년 1월부터 2013년 12월까지 서울 소재 병원에서 첫 번째 열성경련으로 내원하여 진단받은 29,240명의 환아들을 대상으로 시행하였다. 동일기간 동안 기상청에서 수집한 4개의 기상인자(해면기압, 강수량, 습도, 기온) 들과의 연관성을 알아보았다. 포아송 일반화 부가모형(Poisson Generalized Addictive Model)을 이용하였다. 바이러스 감염이 열성 경련의 발생률에 기여하는 영향도 논의되었다. 결과: 강수량은 두 가지 그룹(5 mm 미만과 5 mm 이상)으로 나뉘어 분석되었다. 포아송 분석 결과 열성경련의 발생률은 강수량이 적을수록 증가하였다. 해면기압, 습도, 기온 등 3가지 변수들을 분석하는데 있어서 평활 함수가 사용되었고 그 결과 열성 경련 발생률은 해면기압이 낮을수록, 습도가 낮을수록 증가하였고, 기온이 $-7--1^{\circ}C$와 $18-21^{\circ}C$ 일 때 높았다. 결론: 본 연구는 열성경련과 날씨와의 연관성을 파악하기 위하여 시행되었고, 그 결과 강수량이 적을수록, 해면기압이 낮을수록, 습도가 낮을수록 열성경련의 발생률이 증가하였다. 그러므로, 날씨는 열성경련 발생에 영향을 주는 요인 중 하나이다.