Current computer-aided drug design最新文献

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A new computational approach to the classification of fluoroquinolones according to the Biopharmaceutical Classification System. 根据生物制药分类系统对氟喹诺酮类药物进行分类的新计算方法。

Current computer-aided drug design Pub Date : 2016-10-14

Kłosińska-Szmurło Ewa, Mazurek Aleksander Paweł, Grudzień Monika, Betlejewska-Kielak Katarzyna

{"title":"A new computational approach to the classification of fluoroquinolones according to the Biopharmaceutical Classification System.","authors":"Kłosińska-Szmurło Ewa, Mazurek Aleksander Paweł, Grudzień Monika, Betlejewska-Kielak Katarzyna","doi":"","DOIUrl":"","url":null,"abstract":"Background: Two main factors, which have an influence on oral absorption from solid, immediate release dosage form, are solubility and permeability. These are considered the main fundamental properties that govern the rate and extent of oral absorption. The significance of these properties has been highlighted in the Biopharmaceutics Classification System (BCS).Objective: The concept of this paper was to predict the solubility and permeability of fluoroquinolones using in silico methods based on the assumptions of the BCS. An attempt was also made to determine the place within this system for drugs from the fluoroquinolone group.Method: The study was carried out with the use of modern computational techniques which developed based on Artificial Neural Network Ensembles for Binary Classification.Results: Using the values of the physicochemical descriptors of medicinal compounds with labeled BCS class, two classification models were elaborated for solubility and permeability.Conclusion: The obtained models helped to predict the provisional class for the following drugs in the BCS. Continuous improvement of computational models may support and can be treated equally with the in vivo data.","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":"None"},"PeriodicalIF":0.0,"publicationDate":"2016-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clarification of Interaction Mechanism of Mouse Hepatitis Virus (MHV) N and nsp3 Protein with Homology Modeling and Protein-Protein Docking Analysis. 通过同源建模和蛋白质-蛋白质对接分析阐明小鼠肝炎病毒 (MHV) N 蛋白与 nsp3 蛋白的相互作用机制

Current computer-aided drug design Pub Date : 2016-02-26

Gizem Tatar, Tugba Taskin Tok

{"title":"Clarification of Interaction Mechanism of Mouse Hepatitis Virus (MHV) N and nsp3 Protein with Homology Modeling and Protein-Protein Docking Analysis.","authors":"Gizem Tatar, Tugba Taskin Tok","doi":"","DOIUrl":"","url":null,"abstract":"The coronavirus nucleocapsid (N) plays an important role in the virus structure, the replication, and the transcription of CoV. This protein, which has a helix and flexible structure, and capable of binding on to the viral genomic RNA, is a non-structural protein (nsp3). Many studies suggest that the N protein interaction with nsp3 plays a critical role in the virus replication early in infection. Therefore, it is necessary to know the definition of the interaction mechanism of N and nsp3 protein in terms of the CoV replication transcription mechanism. We report on the homology modeling, molecular dynamics simulation, and docking studies to explain the structure-function relationship and the interaction mechanism. In addition, the prototype MHV is preferred in the wet experiment, so we also based our study on the MHV N and nsp3 proteins that belong to the experimental study. The amino acid sequences of MHV N and nsp3 proteins have similarity between human and severe acute respiratory syndrome coronavirus. Therefore, the 3D structure models of these proteins were built with using the crystal structure of the CoV family members as a template. By following these models, molecular dynamics simulations were applied to attain the most stable conformation. Finally, protein-protein docking was performed to prove accuracy of model structures of the MHV N and to clarify the interaction with nsp3. As a result, Lys 113, Arg 125, Tyr 127, Glu 173, Tyr 190 residues that play an important role in virus replication were determined.","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":"None"},"PeriodicalIF":0.0,"publicationDate":"2016-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

1-R-2-([1,2,4]Triazolo[1,5-c]quinazoline-2-ylthio)etanon(ol)s: synthesis, bioluminescence inhibition, molecular docking studies, antibacterial and antifungal activity. 1-R-2-([1,2,4]三唑并[1,5-c]喹唑啉-2-基硫基)乙二腈：合成、生物发光抑制、分子对接研究、抗菌和抗真菌活性。

Current computer-aided drug design Pub Date : 2016-01-26

Lyudmyla M Antypenko, Sergiy I Kovalenko, Oleksandr V Karpenko, Andrew M Katsev, Volodymyr P Novikov, Natalia S Fedyunina

{"title":"1-R-2-([1,2,4]Triazolo[1,5-c]quinazoline-2-ylthio)etanon(ol)s: synthesis, bioluminescence inhibition, molecular docking studies, antibacterial and antifungal activity.","authors":"Lyudmyla M Antypenko, Sergiy I Kovalenko, Oleksandr V Karpenko, Andrew M Katsev, Volodymyr P Novikov, Natalia S Fedyunina","doi":"","DOIUrl":"","url":null,"abstract":"The increasing mortality due to antibacterial resistance necessitates the search for novel antimicrobial agents. Hence, series of 1-R-2-([1,2,4]triazolo[1,5-c]quinazoline-2-ylthio)etanon(ol)s were synthesized, evaluated by spectral data and studied against St. aureus, M. luteum, E. faecalis, E. aerogenes, P. aeruginosa, C. sakazakii, E.coli, K. pneumonia, hospital Streptococcus spp., C. albicans and A. niger in 100, 500 µg/mL and 100 µg/disk. Substances exhibited moderate toxicity in 0.025, 0.1 and 0.25 mg/mL in bioluminescence inhibition tests of Photobacterium leiognathi. SAR exposed that introduction of 2,4-(Cl)2C6H3-, 2,5-(OMe)2C6H3-, 4-Me-2-iPr-C6H3O- and 3-iPr-C6H4O- fragments and reduction of the pyrimidine ring of R-([1,2,4]triazolo[1,5-c]quinazolin-2-ylthio)alcohols were the best modifications to promote antimicrobial activity. Molecular docking showed their good affinity into the active sites of EcPanK-AMPPNP and hDHFR. Hence, reported results will be used for subsequent QSAR model creation and purposeful antimicrobial modification of the strongest compounds.","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":"None"},"PeriodicalIF":0.0,"publicationDate":"2016-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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