Theoretical Biology and Medical Modelling最新文献_第2页

Annual acknowledgement of manuscript reviewers 稿件审稿人的年度确认

Theoretical Biology and Medical Modelling Pub Date : 2015-07-03 DOI: 10.1186/1742-4682-12-4

H. Nishiura, E. Rietman, Rongling Wu

引用次数: 0

Erratum to: improvement of design of a surgical interface using an eye tracking device 更正:使用眼动追踪装置的手术界面设计的改进

Theoretical Biology and Medical Modelling Pub Date : 2014-11-03 DOI: 10.1186/1742-4682-11-48

D. Barkana, Alper Açik, D. G. Duru, A. Duru

引用次数: 6

Molecular docking studies for the identification of novel melatoninergic inhibitors for acetylserotonin-O-methyltransferase using different docking routines. 采用不同对接方法鉴定新型乙酰- 5 -羟色胺- o -甲基转移酶褪黑素能抑制剂的分子对接研究。

Theoretical Biology and Medical Modelling Pub Date : 2013-10-24 DOI: 10.1186/1742-4682-10-63

Syed Sikander Azam, Sumra Wajid Abbasi

{"title":"Molecular docking studies for the identification of novel melatoninergic inhibitors for acetylserotonin-O-methyltransferase using different docking routines.","authors":"Syed Sikander Azam, Sumra Wajid Abbasi","doi":"10.1186/1742-4682-10-63","DOIUrl":"https://doi.org/10.1186/1742-4682-10-63","url":null,"abstract":"Background: N-Acetylserotonin O-methyltransferase (ASMT) is an enzyme which by converting nor-melatonin to melatonin catalyzes the final reaction in melatonin biosynthesis in tryptophan metabolism pathway. High Expression of ASMT gene is evident in PPTs. The presence of abnormally high levels of ASMT in pineal gland could serve as an indication of the existence of pineal parenchymal tumors (PPTs) in the brain (J Neuropathol Exp Neurol 65: 675-684, 2006). Different levels of melatonin are used as a trait marker for prescribing the mood disorders e.g. Seasonal affective disorder, bipolar disorder, or major depressive disorder. In addition, melatonin levels can also be used to calculate the severity of a patient's illness at a given point in time.Methods: Seventy three melatoninergic inhibitors were docked with acetylserotonin-O-methyltransferase in order to identify the potent inhibitor against the enzyme. The chemical nature of the protein and ligands greatly influence the performance of docking routines. Keeping this fact in view, critical evaluation of the performance of four different commonly used docking routines: AutoDock/Vina, GOLD, FlexX and FRED were performed. An evaluation criterion was based on the binding affinities/docking scores and experimental bioactivities.Results and conclusion: Results indicated that both hydrogen bonding and hydrophobic interactions contributed significantly for its ligand binding and the compound selected as potent inhibitor is having minimum binding affinity, maximum GoldScore and minimum FlexX energy. The correlation value of r2 = 0. 66 may be useful in the selection of correct docked complexes based on the energy without having prior knowledge of the active site. This may lead to further understanding of structures, their reliability and Biomolecular activity especially in connection with bipolar disorders.","PeriodicalId":51195,"journal":{"name":"Theoretical Biology and Medical Modelling","volume":" ","pages":"63"},"PeriodicalIF":0.0,"publicationDate":"2013-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1742-4682-10-63","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40263759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Spatial chaos and complexity in the intracellular space of cancer and normal cells. 癌细胞与正常细胞胞内空间的空间混沌与复杂性。

Theoretical Biology and Medical Modelling Pub Date : 2013-10-24 DOI: 10.1186/1742-4682-10-62

Tuan D Pham, Kazuhisa Ichikawa

{"title":"Spatial chaos and complexity in the intracellular space of cancer and normal cells.","authors":"Tuan D Pham, Kazuhisa Ichikawa","doi":"10.1186/1742-4682-10-62","DOIUrl":"https://doi.org/10.1186/1742-4682-10-62","url":null,"abstract":"Background: One of the most challenging problems in biological image analysis is the quantification of the dynamical mechanism and complexity of the intracellular space. This paper investigates potential spatial chaos and complex behavior of the intracellular space of typical cancer and normal cell images whose structural details are revealed by the combination of scanning electron microscopy and focused ion beam systems. Such numerical quantifications have important implications for computer modeling and simulation of diseases.Methods: Cancer cell lines derived from a human head and neck squamous cell carcinoma (SCC-61) and normal mouse embryonic fibroblast (MEF) cells produced by focused ion beam scanning electron microscopes were used in this study. Spatial distributions of the organelles of cancer and normal cells can be analyzed at both short range and long range of the bounded dynamical system of the image space, depending on the orientations of the spatial cell. A procedure was designed for calculating the largest Lyapunov exponent, which is an indicator of the potential chaotic behavior in intracellular images. Furthermore, the sample entropy and regularity dimension were applied to measure the complexity of the intracellular images.Results: Positive values of the largest Lyapunov exponents (LLEs) of the intracellular space of the SCC-61 were obtained in different spatial orientations for both long-range and short-range models, suggesting the chaotic behavior of the cell. The MEF has smaller positive values of LLEs in the long range than those of the SCC-61, and zero vales of the LLEs in the short range analysis, suggesting a non-chaotic behavior. The intracellular space of the SCC-61 is found to be more complex than that of the MEF. The degree of complexity measured in the spatial distribution of the intracellular space in the diagonal direction was found to be approximately twice larger than the complexity measured in the horizontal and vertical directions.Conclusion: Initial findings are promising for characterizing different types of cells and therefore useful for studying cancer cells in the spatial domain using state-of-the-art imaging technology. The measures of the chaotic behavior and complexity of the spatial cell will help computational biologists gain insights into identifying associations between the oscillation patterns and spatial parameters of cells, and appropriate model for simulating cancer cell signaling networks for cancer treatment and new drug discovery.","PeriodicalId":51195,"journal":{"name":"Theoretical Biology and Medical Modelling","volume":" ","pages":"62"},"PeriodicalIF":0.0,"publicationDate":"2013-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1742-4682-10-62","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40259758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 27

Agent-based modeling of competence phenotype switching in Bacillus subtilis. 枯草芽孢杆菌能力表型转换的agent建模。

Theoretical Biology and Medical Modelling Pub Date : 2013-04-03 DOI: 10.1186/1742-4682-10-23

Suzy M Stiegelmeyer, Morgan C Giddings

{"title":"Agent-based modeling of competence phenotype switching in Bacillus subtilis.","authors":"Suzy M Stiegelmeyer, Morgan C Giddings","doi":"10.1186/1742-4682-10-23","DOIUrl":"https://doi.org/10.1186/1742-4682-10-23","url":null,"abstract":"Background: It is a fascinating phenomenon that in genetically identical bacteria populations of Bacillus subtilis, a distinct DNA uptake phenotype called the competence phenotype may emerge in 10-20% of the population. Many aspects of the phenomenon are believed to be due to the variable expression of critical genes: a stochastic occurrence termed \"noise\" which has made the phenomenon difficult to examine directly by lab experimentation.Methods: To capture and model noise in this system and further understand the emergence of competence both at the intracellular and culture levels in B. subtilis, we developed a novel multi-scale, agent-based model. At the intracellular level, our model recreates the regulatory network involved in the competence phenotype. At the culture level, we simulated growth conditions, with our multi-scale model providing feedback between the two levels.Results: Our model predicted three potential sources of genetic \"noise\". First, the random spatial arrangement of molecules may influence the manifestation of the competence phenotype. In addition, the evidence suggests that there may be a type of epigenetic heritability to the emergence of competence, influenced by the molecular concentrations of key competence molecules inherited through cell division. Finally, the emergence of competence during the stationary phase may in part be due to the dilution effect of cell division upon protein concentrations.Conclusions: The competence phenotype was easily translated into an agent-based model - one with the ability to illuminate complex cell behavior. Models such as the one described in this paper can simulate cell behavior that is otherwise unobservable in vivo, highlighting their potential usefulness as research tools.","PeriodicalId":51195,"journal":{"name":"Theoretical Biology and Medical Modelling","volume":" ","pages":"23"},"PeriodicalIF":0.0,"publicationDate":"2013-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1742-4682-10-23","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40225266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

Structural, phylogenetic and docking studies of D-amino acid oxidase activator (DAOA), a candidate schizophrenia gene. 候选精神分裂症基因--D-氨基酸氧化酶激活剂（DAOA）的结构、系统发育和对接研究。

Theoretical Biology and Medical Modelling Pub Date : 2013-01-04 DOI: 10.1186/1742-4682-10-3

Sheikh Arslan Sehgal, Naureen Aslam Khattak, Asif Mir

{"title":"Structural, phylogenetic and docking studies of D-amino acid oxidase activator (DAOA), a candidate schizophrenia gene.","authors":"Sheikh Arslan Sehgal, Naureen Aslam Khattak, Asif Mir","doi":"10.1186/1742-4682-10-3","DOIUrl":"10.1186/1742-4682-10-3","url":null,"abstract":"Background: Schizophrenia is a neurodegenerative disorder that occurs worldwide and can be difficult to diagnose. It is the foremost neurological disorder leading to suicide among patients in both developed and underdeveloped countries. D-amino acid oxidase activator (DAOA), also known as G72, is directly implicated in the glutamateric hypothesis of schizophrenia. It activates D-amino acid oxidase, which oxidizes D-serine, leading to modulation of the N-methyl-D-aspartate receptor.Methods: MODELLER (9v10) was utilized to generate three dimensional structures of the DAOA candidate gene. The HOPE server was used for mutational analysis. The Molecular Evolutionary Genetics Analysis (MEGA5) tool was utilized to reconstruct the evolutionary history of the candidate gene DAOA. AutoDock was used for protein-ligand docking and Gramm-X and PatchDock for protein-protein docking.Results: A suitable template (1ZCA) was selected by employing BLASTp on the basis of 33% query coverage, 27% identity and E-value 4.9. The Rampage evaluation tool showed 91.1% favored region, 4.9% allowed region and 4.1% outlier region in DAOA. ERRAT demonstrated that the predicted model had a 50.909% quality factor. Mutational analysis of DAOA revealed significant effects on hydrogen bonding and correct folding of the DAOA protein, which in turn affect protein conformation. Ciona was inferred as the outgroup. Tetrapods were in their appropriate clusters with bifurcations. Human amino acid sequences are conserved, with chimpanzee and gorilla showing more than 80% homology and bootstrap value based on 1000 replications. Molecular docking analysis was employed to elucidate the binding mode of the reported ligand complex for DAOA. The docking experiment demonstrated that DAOA is involved in major amino acid interactions: the residues that interact most strongly with the ligand C28H28N3O5PS2 are polar but uncharged (Gln36, Asn38, Thr 122) and non-polar hydrophobic (Ile119, Ser171, Ser21, Ala31). Protein-protein docking simulation demonstrated two ionic bonds and one hydrogen bond involving DAOA. Lys-7 of the receptor protein interacted with Lys-163 and Asp-2037. Tyr-03 interacted with Arg-286 of the ligand protein and formed a hydrogen bond.Conclusion: The predicted interactions might serve to inhibit the disease-related allele. It is assumed that current bioinformatics methods will contribute significantly to identifying, analyzing and curing schizophrenia. There is an urgent need to develop effective drugs for schizophrenia, and tools for examining candidate genes more accurately and efficiently are required.","PeriodicalId":51195,"journal":{"name":"Theoretical Biology and Medical Modelling","volume":" ","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2013-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40209730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Review of ‘BipolART’ by D. N. Wheatley (Springer, 2012) 韦奕礼(d.n. Wheatley)的《双极性艺术》(BipolART)书评(2012年出版)

Theoretical Biology and Medical Modelling Pub Date : 2013-01-03 DOI: 10.1186/1742-4682-10-2

P. Agutter

引用次数: 0

Comparative modeling and docking studies of p16ink4/cyclin D1/Rb pathway genes in lung cancer revealed functionally interactive residue of RB1 and its functional partner E2F1. 肺癌p16ink4/cyclin D1/Rb通路基因的比较建模和对接研究揭示了RB1及其功能伙伴E2F1的功能相互作用残基。

Theoretical Biology and Medical Modelling Pub Date : 2013-01-01 DOI: 10.1186/1742-4682-10-1

Syeda Naqsh e Zahra, Naureen Aslam Khattak, Asif Mir

{"title":"Comparative modeling and docking studies of p16ink4/cyclin D1/Rb pathway genes in lung cancer revealed functionally interactive residue of RB1 and its functional partner E2F1.","authors":"Syeda Naqsh e Zahra, Naureen Aslam Khattak, Asif Mir","doi":"10.1186/1742-4682-10-1","DOIUrl":"https://doi.org/10.1186/1742-4682-10-1","url":null,"abstract":"Background: Lung cancer is the major cause of mortality worldwide. Major signalling pathways that could play significant role in lung cancer therapy include (1) Growth promoting pathways (Epidermal Growth Factor Receptor/Ras/ PhosphatidylInositol 3-Kinase) (2) Growth inhibitory pathways (p53/Rb/P14ARF, STK11) (3) Apoptotic pathways (Bcl-2/Bax/Fas/FasL). Insilico strategy was implemented to solve the mystery behind selected lung cancer pathway by applying comparative modeling and molecular docking studies.Results: YASARA [v 12.4.1] was utilized to predict structural models of P16-INK4 and RB1 genes using template 4ELJ-A and 1MX6-B respectively. WHAT CHECK evaluation tool demonstrated overall quality of predicted P16-INK4 and RB1 with Z-score of -0.132 and -0.007 respectively which showed a strong indication of reliable structure prediction. Protein-protein interactions were explored by utilizing STRING server, illustrated that CDK4 and E2F1 showed strong interaction with P16-INK4 and RB1 based on confidence score of 0.999 and 0.999 respectively. In order to facilitate a comprehensive understanding of the complex interactions between candidate genes with their functional interactors, GRAMM-X server was used. Protein-protein docking investigation of P16-INK4 revealed four ionic bonds illustrating Arg47, Arg80,Cys72 and Met1 residues as actively participating in interactions with CDK4 while docking results of RB1 showed four hydrogen bonds involving Glu864, Ser567, Asp36 and Arg861 residues which interact strongly with its respective functional interactor E2F1.Conclusion: This research may provide a basis for understanding biological insights of P16-INK4 and RB1 proteins which will be helpful in future to design a suitable drug to inhibit the disease pathogenesis as we have determined the interacting amino acids which can be targeted in order to design a ligand in-vitro to propose a drug for clinical trials. Protein -protein docking of candidate genes and their important interacting residues likely to be provide a gateway for developing computer aided drug designing.","PeriodicalId":51195,"journal":{"name":"Theoretical Biology and Medical Modelling","volume":" ","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1742-4682-10-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40198675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 48

Erratum to: modelling the correlation between EGFr expression and tumour cell radiosensitivity, and combined treatments of radiation and monoclonal antibody EGFr inhibitors 校正:模拟EGFr表达与肿瘤细胞放射敏感性之间的相关性，以及放疗和单克隆抗体EGFr抑制剂的联合治疗

Theoretical Biology and Medical Modelling Pub Date : 2012-08-22 DOI: 10.1186/1742-4682-9-37

P. Pedicini, R. Caivano, B. Jereczek-Fossa, L. Strigari, B. Vischioni, D. Alterio, M. Cremonesi, F. Botta, Antonio Nappi, G. Improta, G. Storto, A. Fiorentino, M. Benassi, R. Orecchia, V. Fusco

引用次数: 2

The kinetics of lactate production and removal during whole-body exercise. 全身运动过程中乳酸生成和清除的动力学。

Theoretical Biology and Medical Modelling Pub Date : 2012-03-13 DOI: 10.1186/1742-4682-9-7

John F Moxnes, Øyvind Sandbakk

{"title":"The kinetics of lactate production and removal during whole-body exercise.","authors":"John F Moxnes, Øyvind Sandbakk","doi":"10.1186/1742-4682-9-7","DOIUrl":"10.1186/1742-4682-9-7","url":null,"abstract":"Background: Based on a literature review, the current study aimed to construct mathematical models of lactate production and removal in both muscles and blood during steady state and at varying intensities during whole-body exercise. In order to experimentally test the models in dynamic situations, a cross-country skier performed laboratory tests while treadmill roller skiing, from where work rate, aerobic power and blood lactate concentration were measured. A two-compartment simulation model for blood lactate production and removal was constructed.Results: The simulated and experimental data differed less than 0.5 mmol/L both during steady state and varying sub-maximal intensities. However, the simulation model for lactate removal after high exercise intensities seems to require further examination.Conclusions: Overall, the simulation models of lactate production and removal provide useful insight into the parameters that affect blood lactate response, and specifically how blood lactate concentration during practical training and testing in dynamical situations should be interpreted.","PeriodicalId":51195,"journal":{"name":"Theoretical Biology and Medical Modelling","volume":" ","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2012-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1742-4682-9-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40161622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1