Báo cáo y học: "A danger of low copy numbers for inferring incorrect cooperativity degree"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: A danger of low copy numbers for inferring incorrect cooperativity degree. | Konkoli Theoretical Biology and Medical Modelling 2010 7 40 http content 7 1 40 THEORETICAL BIOLOGY AND MEDICAL MODELLING RESEARCH Open Access A danger of low copy numbers for inferring incorrect cooperativity degree Zoran Konkoli Correspondence zorank@chalmers. se Chalmers University of Technology Department of Microtechnology and Nanoscience Bionano Systems Laboratory Sweden 2 BioMed Central Abstract Background A dose-response curve depicts the fraction of bound proteins as a function of unbound ligands. Dose-response curves are used to measure the cooperativity degree of a ligand binding process. Frequently the Hill function is used to fit the experimental data. The Hill function is parameterized by the value of the dissociation constant and the Hill coefficient which describes the cooperativity degree. The use of Hill s model and the Hill function has been heavily criticised in this context predominantly the assumption that all ligands bind at once which resulted in further refinements of the model. In this work the validity of the Hill function has been studied from an entirely different point of view. In the limit of low copy numbers the dynamics of the system becomes noisy. The goal was to asses the validity of the Hill function in this limit and to see in what ways the effects of the fluctuations change the form of the dose-response curves. Results Dose-response curves were computed taking into account effects of fluctuations. The effects of fluctuations were described at the lowest order the second moment of the particle number distribution by using the previously developed Pair Approach Reaction Noise EStimator PARNES method. The stationary state of the system is described by nine equations with nine unknowns. To obtain fluctuation-corrected dose-response curves the equations have been investigated numerically. Conclusions The Hill function cannot describe dose-response curves in a low particle limit. First dose-response curves are not .

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