• 통합자연과학논문집
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• 제16권1호
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• pp.39-45
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• 2023

P2X receptors are ATP-activated ion channels in the plasma membrane. P2X receptors have a role in a diverse range of disorders, making them a valuable therapeutic target. Hence, the present investigation employed homology modelling of the P2X receptor based on the crystal structure of 5SVJ, 6AH4, 5YVE and 5SVL. Twenty models, using both single- and multiple template-based methods, were developed, and the best model was chosen based on the validation result. We observed that a strategy based on multiple templates provided greater accuracy. Future studies involving binding site and docking analysis can make use of the produced structures.

• BMB Reports
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• 제39권5호
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• pp.578-585
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• 2006

The cDNA of a firefly luciferase from lantern mRNA of Lampyroidea maculata has been cloned, sequenced and functionally expressed. The cDNA has an open reading frame of 1647 bp and codes for a 548-residue-long polypeptide. Noteworthy, sequence comparison as well as homology modeling showed the highest degree of similarity with H. unmunsana and L. mingrelica luciferases, suggesting a close phylogenetic relationship despite the geographical distance separation. The deduced amino acid sequence of the luciferase gene of firefly L. maculata showed 93% identity to H. unmunsana. Superposition of the three-dimensional model of L. maculata luciferase (generated by homology modeling) and three dimensional structure of Photinus pyralis luciferase revealed that the spatial arrangements of Luciferin and ATP-binding residues are very similar. Putative signature of AMP-binding domain among the various firefly species and Lampyroidea maculata was compared and a striking similarity was found. Different motifs and sites have been identified in Lampyroidea maculata by sequence analysis. Expression and purification of luciferase from Lampyroidea maculata was carried out using Ni-NTA Sepharose. Bioluminescence emission spectrum was similar to Photinus pyralis luciferase.

• Bulletin of the Korean Chemical Society
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• 제33권6호
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• pp.1885-1889
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• 2012

Among 23 cytochrome P450s, CYP125A4 was proposed as a putative monooxygenase based on the high level of amino acid sequence homology (54% identity and 75% similarity) with the well characterized C27-steroid $Mycobacterium$ $tuberculosis$ CYP125A1. Utilizing MTBCYP125A1 as a template, homology modeling of SPCYP125A4 was conducted by Accelrys Discovery Studio 3.1 software. The modeled SPCYP125A4 structure with lowest energy value was subsequently assessed for its stereochemical quality and side-chain environment. The final model was generated by showing its active site through the molecular dynamics. The docking of steroids showed broad specificity of SPCYP125A4 with different orientation of ligand within active site facing the heme. One poses of C27-steroid with C26 facing the heme with distance of 3.734 ${\AA}$ from the Fe were predominant.

• Journal of Animal Science and Technology
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• 제57권12호
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• pp.44.1-44.9
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• 2015

Background: Heat shock proteins play an important role in protection from stress stimuli and metabolic insults in almost all organisms. Methods: In this study, computational tools were used to deeply analyse the physicochemical characteristics and, using homology modelling, reliably predict the tertiary structure of the blunt snout bream (Ma-) Hsp70 and Hsc70 proteins. Derived three-dimensional models were then used to predict the function of the proteins. Results: Previously published predictions regarding the protein length, molecular weight, theoretical isoelectric point and total number of positive and negative residues were corroborated. Among the new findings are: the extinction coefficient (33725/33350 and 35090/34840 - Ma-Hsp70/ Ma-Hsc70, respectively), instability index (33.68/35.56 - both stable), aliphatic index (83.44/80.23 - both very stable), half-life estimates (both relatively stable), grand average of hydropathicity (-0.431/-0.473 - both hydrophilic) and amino acid composition (alanine-lysine-glycine/glycine-lysine-aspartic acid were the most abundant, no disulphide bonds, the N-terminal of both proteins was methionine). Homology modelling was performed by SWISS-MODEL program and the proposed model was evaluated as highly reliable based on PROCHECK's Ramachandran plot, ERRAT, PROVE, Verify 3D, ProQ and ProSA analyses. Conclusions: The research revealed a high structural similarity to Hsp70 and Hsc70 proteins from several taxonomically distant animal species, corroborating a remarkably high level of evolutionary conservation among the members of this protein family. Functional annotation based on structural similarity provides a reliable additional indirect evidence for a high level of functional conservation of these two genes/proteins in blunt snout bream, but it is not sensitive enough to functionally distinguish the two isoforms.

• 통합자연과학논문집
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• 제6권4호
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• pp.205-210
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• 2013

Human P-gp is a protein responsible for the multidrug resistance (MDR) and causes failure of cancer chemotherapy. Till date no X-ray crystal structure is reported for this membrane protein, which hampers active research in the field. We performed homology modeling to develop three dimensional (3D) model of P-gp, and docking studies of the verapamil and curcumin have been performed to gain insight into the interaction mechanism between inhibitors and P-gp. It was identified that the inhibitors docked into the upper part of P-gp and interacted through the hydrophobic interactions.

• Bulletin of the Korean Chemical Society
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• 제26권11호
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• pp.1695-1700
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• 2005

Catechol-O-methyltransferase (COMT, EC 2.1.1.6) is an S-adenosylmethionine (SAM, AdoMet) dependent methyltransferase, and is related to the functions of the neurotransmitters in various mental processes, such as Parkinson’s disease. COMT inhibitors represent a new class of antiparkinson drugs, when they are coadministered with levodopa. Based on x-ray structure of rat COMT (rCOMT), the three dimensional structure of human COMT (hCOMT) was constructed by comparative homology modeling using MODELLER. The catalytic site of these two proteins showed subtle differences, but these differences are important to determine the characterization of COMT inhibitor. Ligand docking study is carried out for complex of hCOMT and COMT inhibitors using AutoDock. Among fifteen inhibitors chosen from world patent, nine models were energetically favorable. The average value of heavy atomic RMSD was 1.5 $\AA$. Analysis of ligand-protein binding model implies that Arg201 on hCOMT plays important roles in the interactions with COMT inhibitors. This study may give insight to develop new ways of antiparkinson drug.

• Archives of Pharmacal Research
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• 제29권1호
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• pp.50-58
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• 2006

Translationally controlled tumor protein (TCTP), also known as histamine releasing factor (HRF), is found abundantly in different eukaryotic cell types. The sequence homology of TCTP between different species is very high, belonging to the MSS4/DSS4 superfamily of proteins. TCTP is involved in both cell growth and human late allergy reaction, as well as having a calcium binding property; however, its primary biological functions remain to be clearly elucidated. In regard to many possible functions, the TCTP of Plasmodium falciparum (Pf) is known to bind with an antimalarial agent, artemisinin, which is activated by heme. It is assumed that the endoperoxide-bridge of artemisinin is opened up by heme to form a free radical, which then eventually alkylates, probably to the Cys14 of PfTCTP. Study of the docking of artemisinin with heme, and subsequently with PfTCTP, was carried out to verify the above hypothesis on the basis of structural interactions. The three dimensional (3D) structure of PfTCTP was built by homology modeling, using the NMR structure of the TCTP of Schizosaccharomyces pombe as a template. The quality of the model was examined based on its secondary structure and biological function, as well as with the use of structure evaluating programs. The interactions between artemisinin, heme and PfTCTP were then studied using the docking program, FlexiDock. The center of the peroxide bond of artemisinin and the Fe of heme were docked within a short distance of $2.6{\AA}$, implying the strong possibility of an interaction between the two molecules, as proposed. When the activated form of artemisinin was docked on the PfTCTP, the C4-radical of the drug faced towards the sulfur of Cys14 within a distance of $2.48{\AA}$, again suggesting the possibility of alkylation having occurred. These results confirm the proposed mechanism of the antimalarial effect of artemisinin, which will provide a reliable method for establishing the mechanism of its biological activity using a molecular modeling study.

• 한국정보통신학회논문지
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• 제23권9호
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• pp.1060-1069
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• 2019

보행자 기반의 카메라 자가 보정 방법들은 복잡한 보정 장치나 절차가 필요하지 않기 때문에 비디오 감시 시스템에 적합하다. 하지만 임의 보행자를 보정 대상으로 사용하는 경우 보행자들의 키를 모르기 때문에 보정 정확도가 저하될 수 있다. 본 논문은 실제 감시 환경에서 이 문제를 해결하기 위한 베이지안 보정 방법을 제안한다. 제안하는 방법에서는 감시 지역 사람들의 키에 대한 통계가 있다고 가정하고, 발-머리 호몰로지(foot-head homology)를 사용하여, 발과 머리의 좌표와 보행자 키의 불확실성을 모두 고려하는 확률 모델을 구성한다. 이 확률 모델을 직접 푸는 것은 난해하므로, 본 연구에서는 근사적 방법인 변분 베이지안 추론(variational Bayesian inference)을 사용한다. 따라서, 이를 통해 관측된 보행자들의 키를 추정함과 동시에 정확한 카메라 파라미터를 구할 수 있다. 다양한 실험을 통해 제안된 방법이 노이즈에 강하며, 보정에 대한 정확한 신뢰도를 제공함을 보였다.

• 통합자연과학논문집
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• 제9권2호
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• pp.136-143
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• 2016

KiSS1-derived peptide receptor, a GPCR protein, binds with the hormone kiss peptin. They are important in the neuroendocrine regulation of reproduction and in the secretion of gonadotrophin-releasing hormone. Thus, analysing the structural features of the receptor becomes important. However, the three dimensional structure of the protein is unavailable. Hence in this study, we have performed the homology modelling of KiSS1-derived peptide receptor with 5 different templates. 30 models were constructed using two platforms - Easymodeller and ITasser. The optimal models were chosen based on the model validation. Two models were selected after validation. The developed models could provide useful for analysing the structural features of KiSS1-derived peptide receptor and their pathophysiological role in various disorders related to them.

• 통합자연과학논문집
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• 제11권2호
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• pp.87-92
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• 2018

5-Hydroxytryptamine receptor 7 ($5-HT_7R$) is one of G-Protein coupled receptors, which is found to be involved in the pathophysiology of various neurological disorders including depression, sleep disorders, memory deficiency and neuropathic pain. After activation of $5-HT_7R$ by serotonin, it activates the production of the intracellular signaling molecule cyclic AMP. The availability of 3D structure of the receptor would enhance the development of new drugs. Hence, in the present study, homology modelling of human 5-hydroxytryptamine receptor 7 ($5-HT_7R$) was performed using comparative modelling (Easy Modeller) and threading (I-TASSER) approaches. The generated models were validated using Ramachandran plot and ERRAT plot and the best models were selected based on the validation results. The 3D model developed here could be useful for identifying crucial residues and further docking study.