• 셀메드
• /
• 제3권2호
• /
• pp.12.1-12.4
• /
• 2013

Identification of target protein is an important procedure in the course of drug discovery. Because of complexity, action mechanisms of herbal medicine are rather obscure, unlike small-molecular drugs. Inverse docking simulation is a reverse use of molecular docking involving multiple target searches for known chemical structure. This methodology can be applied in the field of target fishing and toxicity prediction for herbal compounds as well as known drug molecules. The aim of this review is to introduce a series of in silico works for predicting potential drug targets and side-effects based on inverse docking simulations.

• 대한약리학회:학술대회논문집
• /
• 대한약리학회 2006년도 58th Annual Meeting of The Korean Society of Pharmacology
• /
• pp.46-46
• /
• 2006

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
• /
• pp.41-49
• /
• 1994

The most common conventional method of discovering a drug involves a massive screening of a large number of compounds in chemical libraries or in the extracts from natural sources such as plants or microbial broths followed by chemical modification of one or more active compounds to improve their properties as a drug. When the three-dimensional structure of the target molecule for which the drug is searched is known the drug discovery process can be significantly simplified, This is especially true when the three-dimensional structure of a complex between the target and a lead compound is known. In this lecture our experience on the structure-based drug design for human CDK2(cyclin-dependent protein kinase 2) will be discussed with special emphasis on the strength and weakness of this approach of drug discovery. The regulation of the activity of CDK2 plays an important role in the cell proliferation of normal and cancer cells.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권10호
• /
• pp.4301-4305
• /
• 2014

Tanshinone IIA is a pharmacologically active ingredient extracted from Danshen, a Chinese traditional medicine. Its molecular mechanisms are still unclear. The present study utilized computational approaches to uncover the potential targets of this compound. In this research, PharmMapper server was used as the inverse docking tool andnd the results were verified by Autodock vina in PyRx 0.8, and by DRAR-CPI, a server for drug repositioning via the chemical-protein interactome. Results showed that the retinoic acid receptor alpha ($RAR{\alpha}$), a target protein in acute promyelocytic leukemia (APL), was in the top rank, with a pharmacophore model matching well the molecular features of Tanshinone IIA. Moreover, molecular docking and drug repurposing results showed that the complex was also matched in terms of structure and chemical-protein interactions. These results indicated that $RAR{\alpha}$ may be a potential target of Tanshinone IIA for APL. The study can provide useful information for further biological and biochemical research on natural compounds.

• Genomics & Informatics
• /
• 제21권1호
• /
• pp.5.1-5.13
• /
• 2023

Neisseria gonorrhoeae is a Gram-negative aerobic diplococcus bacterium that primarily causes sexually transmitted infections through direct human sexual contact. It is a major public health threat due to its impact on reproductive health, the widespread presence of antimicrobial resistance, and the lack of a vaccine. In this study, we used a bioinformatics approach and performed subtractive genomic methods to identify potential drug targets against the core proteome of N. gonorrhoeae (12 strains). In total, 12,300 protein sequences were retrieved, and paralogous proteins were removed using CD-HIT. The remaining sequences were analyzed for non-homology against the human proteome and gut microbiota, and screened for broad-spectrum analysis, druggability, and anti-target analysis. The proteins were also characterized for unique interactions between the host and pathogen through metabolic pathway analysis. Based on the subtractive genomic approach and subcellular localization, we identified one cytoplasmic protein, 2Fe-2S iron-sulfur cluster binding domain-containing protein (NGFG RS03485), as a potential drug target. This protein could be further exploited for drug development to create new medications and therapeutic agents for the treatment of N. gonorrhoeae infections.

• 한국약용작물학회:학술대회논문집
• /
• 한국약용작물학회 2012년도 심포지엄 및 춘계학술발표회
• /
• pp.1-2
• /
• 2012

• 통합자연과학논문집
• /
• 제5권4호
• /
• pp.216-219
• /
• 2012

Structure-based drug design possibly benefit from in silico methods that precisely predict the binding affinity of small molecules to target macromolecules. There are many limitations arise from the difficulty of predicting the binding affinity of a small molecule to a biological target with the current scoring functions. There is thus a strong interest in novel methodologies based on MD simulations that claim predictions of greater accuracy than current scoring functions, helpful for a regular use designed for drug discovery in the pharmaceutical industry. Herein, we report a short review on free energy calculations using MMPBSA method a useful method in structure based drug discovery.

• 한국컴퓨터정보학회논문지
• /
• 제21권1호
• /
• pp.115-123
• /
• 2016

In this study, we collect various side effect pairs which are appeared frequently at many drugs, and select side effect pairs that have higher severity. For every selected side effect pair, we extract common genetic networks which are shared by side effects' genes and drugs' target genes based on PPI(Protein-Protein Interaction) network. For this work, firstly, we gather drug related data, side effect data and PPI data. Secondly, for extracting common genetic network, we find shortest paths between drug target genes and side effect genes based on PPI network, and integrate these shortest paths. Thirdly, we develop a classification model which uses this common genetic network as a classifier. We calculate similarity score between the common genetic network and genetic network of a drug for classifying the drug. Lastly, we validate our classification model by means of AUC(Area Under the Curve) value.

• BMB Reports
• /
• 제56권11호
• /
• pp.606-611
• /
• 2023

The main protease (Mpro) of SARS-CoV-2 cleaves 11 sites of viral polypeptide chains and generates essential non-structural proteins for viral replication. Mpro is an important drug target against COVID-19. In this study, we developed a real-time fluorometric turn-on assay system to evaluate Mpro proteolytic activity for a substrate peptide between NSP4 and NSP5. It produced reproducible and reliable results suitable for HTS inhibitor assays. Thus far, most inhibitors against Mpro target the active site for substrate binding. Mpro exists as a dimer, which is essential for its activity. We investigated the potential of the Mpro dimer interface to act as a drug target. The dimer interface is formed of domain II and domain III of each protomer, in which N-terminal ten amino acids of the domain I are bound in the middle as a sandwich. The N-terminal part provides approximately 39% of the dimer interface between two protomers. In the real-time fluorometric turn-on assay system, peptides of the N-terminal ten amino acids, N10, can inhibit the Mpro activity. The dimer interface could be a prospective drug target against Mpro. The N-terminal sequence can help develop a potential inhibitor.

• Archives of Pharmacal Research
• /
• 제29권7호
• /
• pp.598-604
• /
• 2006

In many conventional drug delivery systems in vogue, failure to deliver efficient drug delivery at the target site/organs; is evident as a result, less efficacious pharmacological response is elicited. Microspheres can be derived a remedial measure which can improve site-specific drug delivery to a considerable extent. As an application, Lung-targeting Ofloxacin-loaded gelatin microspheres (GLOME) were prepared by water in oil emulsion method. The Central Composite Design (CCD) was used to optimize the process of preparation, the appearance and size distribution were examined by scanning electron microscopy, the aspects such as in vitro release characteristics, stability, drug loading, loading efficiency, pharmacokinetics and tissue distribution in albino mice were studied. The experimental results showed that the microspheres in the range of $0.32-22\;{\mu}m$. The drug loading and loading efficiency were 61.05 and 91.55% respectively. The in vitro release profile of the microspheres matched the korsmeyer’s peppas release pattern, and release at 1h was 42%, while for the original drug, ofloxacin under the same conditions 90.02% released in the first half an hour. After i.v. administration (15 min), the drug concentration of microspheres group in lung in albino mice was $1048\;{\mu}g/g$, while that of controlled group was $6.77\;{\mu}g/g$. GLOME found to release the drug to a maximum extent in the target tissue, lungs.