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Adaptive torsion-angle quasi-statics: a general simulation method with applications to protein structure analysis and design 总被引:1,自引:0,他引:1
Rossi R Isorce M Morin S Flocard J Arumugam K Crouzy S Vivaudou M Redon S 《Bioinformatics (Oxford, England)》2007,23(13):i408-i417
MOTIVATION: The cost of molecular quasi-statics or dynamics simulations increases with the size of the simulated systems, which is a problem when studying biological phenomena that involve large molecules over long time scales. To address this problem, one has often to either increase the processing power (which might be expensive), or make arbitrary simplifications to the system (which might bias the study). RESULTS: We introduce adaptive torsion-angle quasi-statics, a general simulation method able to rigorously and automatically predict the most mobile regions in a simulated system, under user-defined precision or time constraints. By predicting and simulating only these most important regions, the adaptive method provides the user with complete control on the balance between precision and computational cost, without requiring him or her to perform a priori, arbitrary simplifications. We build on our previous research on adaptive articulated-body simulation and show how, by taking advantage of the partial rigidification of a molecule, we are able to propose novel data structures and algorithms for adaptive update of molecular forces and energies. This results in a globally adaptive molecular quasi-statics simulation method. We demonstrate our approach on several examples and show how adaptive quasi-statics allows a user to interactively design, modify and study potentially complex protein structures. 相似文献
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Stephen S. H. Huang David Banner Norbert Degousee Alberto J. Leon Louling Xu Stephane G. Paquette Thirumagal Kanagasabai Yuan Fang Salvatore Rubino Barry Rubin David J. Kelvin Alyson A. Kelvin 《Journal of virology》2012,86(24):13187-13201
Young children are typically considered a high-risk group for disease associated with influenza virus infection. Interestingly, recent clinical reports suggested that young children were the smallest group of cases with severe pandemic 2009 H1N1 (H1N1pdm) influenza virus infection. Here we established a newly weaned ferret model for the investigation of H1N1pdm infection in young age groups compared to adults. We found that young ferrets had a significantly milder fever and less weight loss than adult ferrets, which paralleled the mild clinical symptoms in the younger humans. Although there was no significant difference in viral clearance, disease severity was associated with pulmonary pathology, where newly weaned ferrets had an earlier pathology improvement. We examined the immune responses associated with protection of the young age group during H1N1pdm infection. We found that interferon and regulatory interleukin-10 responses were more robust in the lungs of young ferrets. In contrast, myeloperoxidase and major histocompatibility complex responses were persistently higher in the adult lungs; as well, the numbers of inflammation-prone granulocytes were highly elevated in the adult peripheral blood. Importantly, we observed that H1N1pdm infection triggered formation of lung structures that resembled inducible bronchus-associated lymphoid tissues (iBALTs) in young ferrets which were associated with high levels of homeostatic chemokines CCL19 and CXCL13, but these were not seen in the adult ferrets with severe disease. These results may be extrapolated to a model of the mild disease seen in human children. Furthermore, these mechanistic analyses provide significant new insight into the developing immune system and effective strategies for intervention and vaccination against respiratory viruses. 相似文献
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Grimaud R Ghiglione JF Cagnon C Lauga B Vaysse PJ Rodriguez-Blanco A Mangenot S Cruveiller S Barbe V Duran R Wu LF Talla E Bonin P Michotey V 《Journal of bacteriology》2012,194(13):3539-3540
Marinobacter hydrocarbonoclasticus SP17 forms biofilms specifically at the interface between water and hydrophobic organic compounds (HOCs) that are used as carbon and energy sources. Biofilm formation at the HOC-water interface has been recognized as a strategy to overcome the low availability of these nearly water-insoluble substrates. Here, we present the genome sequence of SP17, which could provide further insights into the mechanisms of enhancement of HOCs assimilation through biofilm formation. 相似文献
189.
Lunn G Roberts LR Content S Critcher DJ Douglas S Fenwick AE Gethin DM Goodwin G Greenway D Greenwood S Hall K Thomas M Thompson S Williams D Wood G Wylie A 《Bioorganic & medicinal chemistry letters》2012,22(6):2200-2203
3-Azabicyclo[3.1.0]hexane compounds were designed as novel achiral μ opioid receptor ligands for the treatment of pruritus in dogs. In this paper, we describe the SAR of this class of opioid ligand, highlighting changes to the lead structure which led to compounds having picomolar binding affinity, selective for the μ receptor over δ and κ subtypes. Some subtleties of functional activity will also be described. 相似文献
190.
Glucose and lipid metabolism in the pancreas of rainbow trout is regulated at the molecular level by nutritional status and carbohydrate intake 总被引:1,自引:0,他引:1
Polakof S Skiba-Cassy S Kaushik S Seiliez I Soengas JL Panserat S 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2012,182(4):507-516
Glucose and lipid metabolism in pancreatic islet organs is poorly characterized. In the present study, using as a model the
carnivorous rainbow trout, a glucose-intolerant fish, we assessed mRNA expression levels of several genes involved in glucose
and lipid metabolism (including ATP-citrate lyase; carnitine palmitoyltransferase-1 isoforms, CPT; the mitochondrial isoform
of the phosphoenolpyrutave carboxykinase, mPEPCK and pyruvate kinase, PK) and glucosensing (glucose transporter type 2, Glut2; glucokinase,
GK and the potassium channel, KATP) in Brockmann bodies. We evaluated the response of these parameters to changes in feeding status (food deprived vs. fed fish)
as well as to changes in the amount of carbohydrate (dextrin) in the diet. A general inhibition of the glycolytic (including
the glucosensing marker GK) and β-oxidation pathways was found when comparing fed versus food-deprived fish. When comparing
fish feeding on either low- or high-carbohydrate diets, we found that some genes related to lipid metabolism were more controlled
by the feeding status than by the carbohydrate content (fatty acid synthase, CPTs). Findings are discussed in the context
of pancreatic regulation of glucose and lipid metabolism in fish, and show that while trout pancreatic metabolism can partially
adapt to a high-carbohydrate diet, some of the molecular actors studied seem to be poorly regulated (KATP) and may contribute to the glucose intolerance observed in this species when fed high-carbohydrate diets. 相似文献