• 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.203-209
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• 2004

Molecular docking using Lamarckian genetic algorithm of AutoDock 3.0 (AD3) was employed to understand in retrospect the selectivity of phenylaminopyrimidine (PAP) derivatives against the kinase domain c-Abl, implicated in chronic myelogenous leukemia (CML). The energetics of protein-ligand complex was scored using AD3 to identify active drug conformations while Ligplot and ligand protein contact (LPC) programs were used to probe schematic molecular recognition of the bound inhibitor to the protein. Results signify correlation between model and crystal structures of STI-571 compound or Imatinib (IM), a PAP derivative and now clinically proven for its efficacy in CML. A prospect active form Abl inhibitor scaffold from matlystatin class of compounds will be published elsewhere.

• 한국결정학회:학술대회논문집
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• 한국결정학회 2003년도 춘계학술연구발표회
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• pp.14-14
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• 2003

We have crystallized and determined the structures o the Shank PDZ domain, alone and in complex with the synthetic C-terminal hexapeptide of GKAP protein at resolutions of 1.8Å and 2.5Å, respectively. The structure revealed the structural basis of the ligand recongition by Class I PDZ-ligand interaction. Moreover, dimeric structureof shank PDZ domain suggests that the βA strand is a common surface for dimerization of PDZ domains.

• 통합자연과학논문집
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• 제3권1호
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• pp.49-53
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• 2010

Molecular docking is a critical event which mostly forms Van der waals complex in molecular recognition. Since the majority of developed drugs are small molecules, docking them into proteins has been a prime concern in drug discovery community. Since the binding pose space is too vast to cover completely, many search algorithms such as genetic algorithm, Monte Carlo, simulated annealing, distance geometry have been developed. Proper evaluation of the quality of binding is an essential problem. Scoring functions derived from force fields handle the ligand binding prediction with the use of potential energies and sometimes in combination with solvation and entropy contributions. Knowledge-based scoring functions are based on atom pair potentials derived from structural databases. Forces and potentials are collected from known protein-ligand complexes to get a score for their binding affinities (e.g. PME). Empirical scoring functions are derived from training sets of protein-ligand complexes with determined affinity data. Because non of any single scoring function performs generally better than others, some other approaches have been tried. Although numerous scoring functions have been developed to locate the correct binding poses, it still remains a major hurdle to derive an accurate scoring function for general targets. Recently, consensus scoring functions and target specific scoring functions have been studied to overcome the current limitations.

• Archives of Pharmacal Research
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• 제21권4호
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• pp.423-428
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• 1998

The ligand binding signals to a wide variety of seven transmembrane cell surface receptors are transduced into intracellular signals through heterotrimeric G-proteins. Recently, there have been reports which show diverse coupling patterns of ligand-activated receptors to the members of Gq family $\alpha$ subunits. In order to shed some light on these complex signal processing networks, interactions between G$\alpha$q family of G protein and neurokinin-2 receptor as well as muscarinic M$_{1}$ receptor, which are considered to be new thearpeutic targets in asthma, were studied. Using washed membranes from Cos-7 cells co-transfected with different G.alpha.q and receptor cDNAs, the receptors were stimulated with various concentrations of carbachol and neurokinin A and the agonist-dependent release of [$^3H$]inositol phosphates through phospholipase C beta-1 activation was measured. Differential coupling of Gaq family of G-protein to muscarinic M$_{1}$ receptor and neurokinin-2 receptor was observed. The neurokinin-2 receptor shows a ligand-mediated response in membranes co-transfected with G$\alpha$q, G$\alpha$11 and G$\alpha$14 but not G$\alpha$16 and the ability of the muscarinic $M_1$ receptor to activate phospholipase C through G$\alpha$/11 but not G$\alpha$14 and G$\alpha$16 was demonstrated. Clearly G$\alpha$/11 can couple $\M_1$ and neurokinin-2 receptor to activate phospholipase C. But, there are differences in the relative coupling of the G$\alpha$14 and G$\alpha$16 subunits to these receptors.

• 통합자연과학논문집
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• 제10권3호
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• pp.125-130
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• 2017

Glucagon like pepide-2, one of the GLPs, is involved in various metabolic functions in the gastrointestinal tract. It plays a major role in the regulation of mucosal epithelium and the intestinal crypt cell proliferation. Because of their therapeutic importance towards the diseases in the gastrointestinal tract, it becomes necessary to study their interaction with its receptor, GLP-2R. In this study, we have developed protein-protein docking complexes of GLP-2 - GLP-2 receptor. Homology models of GLP-2 are developed, and a reliable model out of the predicted models was selected after model validation. The model was bound with the receptor, to study the important interactions of the complex. This study could be useful in developing novel and potent drugs for the diseases related with GLP-2.

• Biomolecules & Therapeutics
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• 제25권1호
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• pp.4-11
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• 2017

Heterotrimeric G proteins are key intracellular coordinators that receive signals from cells through activation of cognate G protein-coupled receptors (GPCRs). The details of their atomic interactions and structural mechanisms have been described by many biochemical and biophysical studies. Specifically, a framework for understanding conformational changes in the receptor upon ligand binding and associated G protein activation was provided by description of the crystal structure of the ${\beta}2$-adrenoceptor-Gs complex in 2011. This review focused on recent findings in the conformational dynamics of G proteins and GPCRs during activation processes.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.3817-3825
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• 2015

Background: The human protein methyl-transferase DOT1L catalyzes the methylation of histone H3 on lysine 79 (H3K79) at homeobox genes and is also involved in a number of significant processes ranging from gene expression to DNA-damage response and cell cycle progression. Inhibition of DOT1L activity by shRNA or small-molecule inhibitors has been established to prevent proliferation of various MLL-rearranged leukemia cells in vitro, establishing DOT1L an attractive therapeutic target for mixed lineage leukemia (MLL). Most of the drugs currently in use for the MLL treatment are reported to have low efficacy, hence this study focused on various natural compounds which exhibit minimal toxic effects and high efficacy for the target receptor. Materials and Methods: Structures of human protein methyl-transferase DOT1L and natural compound databases were downloaded from various sources. Virtual screening, molecular docking, dynamics simulation and drug likeness studies were performed for those natural compounds to evaluate and analyze their anti-cancer activity. Results: The top five screened compounds possessing good binding affinity were identified as potential high affinity inhibitors against DOT1L's active site. The top ranking molecule amongst the screened ligands had a Glide g-score of -10.940 kcal/mol and Glide e-model score of -86.011 with 5 hydrogen bonds and 12 hydrophobic contacts. This ligand's behaviour also showed consistency during the simulation of protein-ligand complex for 20000 ps, which is indicative of its stability in the receptor pocket. Conclusions: The ligand obtained out of this screening study can be considered as a potential inhibitor for DOT1L and further can be treated as a lead for the drug designing pipeline.

• 한국균학회지
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• 제16권3호
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• pp.121-127
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• 1988

흰느타리버섯(Pleurotus cornucopiae(Per.) Rolland)중의 단백질을 선택적으로 분리정제하기 위하여 AH-Sepharose 4B를 출발 물질로 하여 benzoyl-AH-Sepharose 4B를 합성하여 친화성 크로마토그래피하였다. 1) AH-Sepharose 4B 중의 amino기의 capacity는 겔 Iml 당 $9.5{\mu}mol$ 이었으며 합성겔의 리간드인 benzoyl기의 capacity는 겔 1ml당 $9.3{\mu}mol4이었다. 2) 친화성이 있는 단백질의 총 겉보기 분자량은 255,000 돌톤 이었으며, 이는 29,500, 31,500, 34,000, 71,000 및 89,000돌톤 단백질의 복합체였다. 3) 친화성 단백질 중의 아미노산 함량은 비극성 아미노산이 45.68%, 극성 아미노산이 26.93%, 양성 아미노산이 11.81%, 그리고 음성 아미노산이15.58%였다. 4) 소수성 benzoyl기에 친화성이 있는 단백질은 비극성인 것이 선택적으로 분리되었다.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.359.3-359.3
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• 2002

Protein-tyrosine phosphatase 1 B(PTP-l B). which plays a key role in insulin signaling. is rising as a fascinating target for type 2 diabetes and obesity. Many scientists in structural biology solved the three dimensional X-ray Crystal structure of this type of enzyme, so we could easily get the active site structure of PTP-1 B or complex structure with ligand. Our virtual screening study for PTP-1B exactly based on these crystal strucutures from public database. (omitted)

• 제어로봇시스템학회:학술대회논문집
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• 제어로봇시스템학회 2002년도 ICCAS
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• pp.77.1-77
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• 2002

Platelets arrest bleeding and repair damaged blood vessels. The purpose of this paper is to formulate a mathematical model for the control of platelet adhesion within the vasculature consistent with experimental findings, particularly those of Frenette, Ruggeri , Savage, Yuan, Lawrence and Springer. In addition to providing some, albeit rudimentary, insight into the behavior of platelets, a numerical simulation of this theoretical model may be useful in a systematic study of pathological cases. Glycoprotein receptor complex (GPIb/V/IX), found on the platelet surface membrane, binds to the adhesive protein and ligand von Willebrand factor (vWf), located within the sub-endothelium. The binding...