• 한국생물정보학회:학술대회논문집
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• 한국생물정보시스템생물학회 2005년도 BIOINFO 2005
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• pp.134-138
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• 2005

The design of ion channel targeted library is a valuable methodology that can aid in the selection and prioritization of potential ion channel-likeness for ion-channel-targeted bio-screening from large commercial available chemical pool. The differences of property profiling between the 93 ion-channel active compounds from MDDR and CMC database and the ACDSC compounds were classified by suitable descriptors calculated with preADME software. Through the PCA, clustering, and similarity analysis, the compounds capable of ion channel activity were defined in ACDSC compounds pool. The designed library showed a tendency to follow the property profile of ion-channel active compounds and can be implemented with great time and economical efficiencies of ligand-based drug design or virtual high throughput screening from an enormous small molecule space.

• 한국생물정보학회:학술대회논문집
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• 한국생물정보시스템생물학회 2004년도 The 3rd Annual Conference for The Korean Society for Bioinformatics Association of Asian Societies for Bioinformatics 2004 Symposium
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• pp.210-218
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• 2004

Poly(ADP-ribose)polymerase-1 (PARP-1) is a nuclear enzyme involved in various physical functions related to genomic repair, and PARP inhibitors have therapeutic application in a variety of neurological diseases. Docking and the QSAR (quantitative structure-activity relationships) studies for 52 PARP-1 inhibitors were conducted using FlexX algorithm, comparative molecular field analysis (CoMFA), and hologram quantitative structure-activity relationship analysis (HQSAR). The resultant FlexX model showed a reasonable correlation (r$^{2}$ = 0.701) between predicted activity and observed activity. Partial least squares analysis produced statistically significant models with q$^{2}$ values of 0.795 (SDEP=0.690, r$^{2}$=0.940, s=0.367) and 0.796 (SDEP=0.678, r$^{2}$ = 0.919, s=0.427) for CoMFA and HQSAR, respectively. The models for the entire inhibitor set were validated by prediction test and scrambling in both QSAR methods. In this work, combination of docking, CoMFA with 3D descriptors and HQSAR based on molecular fragments provided an improved understanding in the interaction between the inhibitors and the PARP. This can be utilized for virtual screening to design novel PARP-1 inhibitors.

• Bulletin of the Korean Chemical Society
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• 제32권12호
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• pp.4341-4346
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• 2011

Impact sensitivity, one of the most important screening factors for novel high energy density materials (HEDMs), was predicted by use of quantitative structure-property relationship (QSPR) based on the electrostatic potential (ESP) values calculated on the van der Waals molecular surface (MSEP). Among various 3D descriptors derived from MSEP, we utilized total and positive variance of MSEP, and devised a new QSPR equation by combining three other parameters. We employed 37 HEDMs bearing a benzene scaffold and nitro substituents, which were also utilized by Rice and Hare. All the molecular structures were optimized at the B3LYP/6-31G(d) level of theory and confirmed as minima by the frequency calculations. Our new QSPR equation provided a good result to predict the impact sensitivities of the molecules in the training set including zwitterionic molecules.

• 대한화학회지
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• 제55권5호
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• pp.733-740
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• 2011

Multiple regression analysis was used for the calculation of pKa values of 15 substituted benzaldoximes by using various types of descriptors as parameters. These descriptors are based on quantum mechanical treatments. They were derived by employing semi-empirical calculation represented by the PM3 model and an Abinitio method expressed by Hartree-Fock(HF) model performed at the 6-311 G(d, p) level of theory. The parameters tested for their ability to represent the variations observed in the experimental pKa(s) are atomic and structural properties including Muliken charges on the atoms of hydroxyl group and C=N bond, the angle $C_6-C_1-C_7$, and length of O-H bond. Molecular properties are also used like energies of HOMO and LUMO, hardness(${\eta}$), chemical potential(${\mu}$), total energy(TE), dipole of molecule(DM), and electrophilicity index(W). The relation between pKa values and each of these parameters of the studied compounds is investigated. Depending on these relations, two sets of parameters were constructed for comparison between the PM3 and HF methods. The results obtained favor the Abinitio method for such applications although both models proved to have high predictive power and have sufficient reliability to describe the effect of substituents on pKa values of benzaldoxime compounds under consideration which is clear from the values of correlation coefficient $R^2$ obtained and the consistency between the experimental and the calculated values.

• Bulletin of the Korean Chemical Society
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• 제33권5호
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• pp.1527-1535
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• 2012

Selection of the most informative molecular descriptors from the original data set is a key step for development of quantitative structure activity/property relationship models. Recently, mutual information (MI) has gained increasing attention in feature selection problems. This paper presents an effective mutual information-based feature selection approach, named mutual information maximization by replacing collinear variables (MIMRCV), for nonlinear quantitative structure-property relationship models. The proposed variable selection method was applied to three different QSPR datasets, soil degradation half-life of 47 organophosphorus pesticides, GC-MS retention times of 85 volatile organic compounds, and water-to-micellar cetyltrimethylammonium bromide partition coefficients of 62 organic compounds.The obtained results revealed that using MIMRCV as feature selection method improves the predictive quality of the developed models compared to conventional MI based variable selection algorithms.

• Bulletin of the Korean Chemical Society
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• 제32권11호
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• pp.3865-3872
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• 2011

A quantitative structure-property relationship (QSPR) study was performed for the prediction of the absorption maxima of azobenzene dyes. The entire set of 191 azobenzenes was divided into a training set of 150 azobenzenes and a test set of 41 azobenzenes according to Kennard and Stones algorithm. A seven-descriptor model, with squared correlation coefficient ($R^2$) of 0.8755 and standard error of estimation (s) of 14.476, was developed by applying stepwise multiple linear regression (MLR) analysis on the training set. The reliability of the proposed model was further illustrated using various evaluation techniques: leave-many-out crossvalidation procedure, randomization tests, and validation through the test set.

• 대한화학회지
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• 제44권6호
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• pp.501-506
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• 2000

탄화수소의 생성엔탈피를 예측하는 이전의 선형방정식들을 일반화하였다. QSPR 분석에서 사용된 분자를 표현하는 기본적인 인자는 원자와 화학결합이다. 이러한 선택은 이 방법을 매우 간단하게 하며 비용을 줄일 수 있게 한다. 19개의 알켄에 대한 예측치는 실험오차 정도의 편차를 준다. 이 방법의 몇몇 가능한 확장에 대해 지적하였다.

• Bulletin of the Korean Chemical Society
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• 제24권12호
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• pp.1757-1762
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• 2003

The interrelation between retention factors of several L-amino acids and their physico-chemical and structural properties can be determined in chromatographic research. In this paper we describe a predictor for retention factors with various properties of the L-amino acids. Eighteen L-amino acids are included in this study, and retention factors are measured experimentally by RP-HPLC. Binding energy ($E_b$), hydrophobicity (log P), molecular refractivity (MR), polarizability (${\alpha}$), total energy ($E_t$), water solubility (log S), connectivity index (${\chi}$) of different orders and Wiener index (w) are theoretically calculated. Relationships between these properties and retention factors are established, and their predictive and interpretive ability are evaluated. The equation of the relationship between retention factors and various descriptors of L-amino acids is suggested as linear and multiple linear form, and the correlation coefficients estimated are relatively higher than 0.90.

• 대한화학회지
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• 제54권4호
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• pp.363-373
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• 2010

마약인 모르핀, 헤로인, 코데인, 펜타조신 그리고, 버프레노파인에 대하여 범밀도함수이론에 근거하여 계산 연구를 수행하였다. 약물특이 분자단과 치환기의 기하학적 파라미터는 B3LYP/6-31+G(d) 레벨로 계산하였고, 전자의 구조는B3LYP/6-311++G(d,p) 레벨로 같은 혼성 범함수를 사용하여 계산하였다. 원자의 전하분포는 Mulliken 개체 수 분석에 의하여 구하였다. 보고된 생물학적 활성, 계산된 분배 계수, 전자 및 기하학적 분석을 토대로 펜타조신과 버프레노파인을 새로 제시된 유사화합물에 대한 모델화합물로 선택하였으며, 이들 유사화합물에 대하여 연구한 뒤, 모델화합물과 비교하였다. 본 연구 결과는 약물특이 분자단의 기하학적 구조와 전자 구조가 다른 치환기의 존재 하에서도 변함없이 유지된다는 것을 보여주었다. 제시된 유사화합물들도 모델 분자의 특성을 갖고 있기 때문에, 이들 유사화합물들도 생물학적 활성을 나타낼 것 같다.

• Bulletin of the Korean Chemical Society
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• 제29권3호
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• pp.647-655
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• 2008

Microsomal prostaglandin E2 synthase (mPGES-1) is a potent target for pain and inflammation. Various QSAR (quantitative structure activity relationship) analyses used to understand the factors affecting inhibitory potency for a series of MK886 analogues. We derived four QSAR models utilizing various quantum mechanical (QM) descriptors. These QM models indicate that steric, electrostatic and hydrophobic interaction can be important factors. Common pharmacophore hypotheses (CPHs) also have studied. The QSAR model derived by best-fitted CPHs considering hydrophobic, negative group and ring effect gave a reasonable result (q2 = 0.77, r2 = 0.97 and Rtestset = 0.90). The pharmacophore-derived molecular alignment subsequently used for 3D-QSAR. The CoMFA (Comparative Molecular Field Analysis) and CoMSIA (Comparative Molecular Similarity Indices Analysis) techniques employed on same series of mPGES-1 inhibitors which gives a statistically reasonable result (CoMFA; q2 = 0.90, r2 = 0.99. CoMSIA; q2 = 0.93, r2 = 1.00). All modeling results (QM-based QSAR, pharmacophore modeling and 3D-QSAR) imply steric, electrostatic and hydrophobic contribution to the inhibitory activity. CoMFA and CoMSIA models suggest the introduction of bulky group around ring B may enhance the inhibitory activity.