From owner-biophys@hgmp.mrc.ac.uk Tue May 9 17:46:30 2000 Return-Path: Received: by mercury.hgmp.mrc.ac.uk (Postfix, from userid 110) id 80E0217AD4; Tue, 9 May 2000 17:46:29 +0100 (BST) Received: from niobium.hgmp.mrc.ac.uk (niobium [193.62.192.41]) by hgmp.mrc.ac.uk (8.9.3/8.9.3) with ESMTP id RAA23439 for ; Tue, 9 May 2000 17:46:26 +0100 (BST) Received: (from news@localhost) by niobium.hgmp.mrc.ac.uk (8.9.3+Sun/8.8.8) id RAA17735 for biophys-list@hgmp.mrc.ac.uk; Tue, 9 May 2000 17:46:25 +0100 (BST) X-Authentication-Warning: niobium.hgmp.mrc.ac.uk: news set sender to using -f From: Petr Kuzmic X-Newsgroups: bionet.biophysics Subject: Re: [ANN] Freeware for biochemical kinetics and equilibria Date: Tue, 09 May 2000 11:48:29 -0500 Organization: BioKin Ltd. [http://www.biokin.com] Lines: 170 Message-ID: <3918415D.37CAB3FA@biokin.com> References: <39181C00.F82A6B4F@biokin.com> <8f9db4$a6uci$1@fu-berlin.de> Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit X-Trace: news.chorus.net 957890761 22870 216.165.150.162 (9 May 2000 16:46:01 GMT) X-Complaints-To: abuse@chorus.net X-Mailer: Mozilla 4.72 [en] (WinNT; U) X-Accept-Language: en To: biophys@hgmp.mrc.ac.uk Sender: owner-biophys@hgmp.mrc.ac.uk Precedence: bulk Frank Fuerst wrote: > > Petr Kuzmic wrote: > > > > > > 1. DynaFit version upgrade > > -------------------------- > > The freeware program DynaFit [P. Kuzmic (1996) Anal. Biochem. 237, > > 260-173] has been updated to version 3.21 and is now available for > > download from the BioKin website. > > With DynaFit, is it possible to do analyze multiple datasets > simultaneously, e.g. kinetic and equilibrium data on several connected > reactions, or sequential reactions monitored by different signals, > each containing information about more than one of the phases? There are some portions of your question that I don't fully understand, but I'll try to answer as best as I can: ----- "Is it possible to do analyze multiple datasets simultaneously": ----- The answer is 'yes'. DynaFit can analyze multiple datasets treated as one 'super-set' of data. Some datasets in this 'super-set' can have adjustable parameters associated with them that are *local*, or characteristic only for the given dataset. For example, each dataset in the 'super-set' can have its own baseline offset or instrument response constant. On the other hand, other adjustable parameters are treated as *global* to the entire 'super-set' of data, i.e., a collection of datasets. For example, rate constants always are treated as global parameters, characteristic for the entire super-set of datasets. Sometimes people talk about "global analysis" in this case. ----- "...kinetic and equilibrium data": ----- If you could give an example, that would be useful, but if I understand you correctly the answer is 'yes', DynaFit can treat kinetic *and* equilibrium data in the same problem. For example, a chemical and biochemical mixture [e.g., enzyme + reversible inhibitor] could be initially allowed to achieve its equilibrium composition, characterized by some (as yet unknown) *equilibrium* constants. Call this the "equilibrium phase" of the experiment. Then the biochemical mixture is perturbed by adding some other reactant [e.g., substrate] after which the composition changes over time. Call this the "kinetic phase" of the experiment. DynaFit can analyze this kind of "hybrid" (equilibrium + kinetic) experiment. ----- "... on several connected reactions, or sequential reactions": ----- Yes, you can have an arbitrary mechanism treated by DynaFit, as long as it does not include 'fractional order' steps. In other words, we can have first-order, second-order, or zero-order [constant influx or efflux] elementary steps. The most complicated and *realistic* mechanism, included in the program distribution, is the mechanism taken from the blood coagulation cascade. You can see it at the end of this message. ----- "... monitored by different signals": ----- Yes. You can analyze simultaneously several datasets that were obtained by monitoring e.g. at different wavelengths in a time-resolved spectroscopic experiment. Each of the experimental signals can be sensitive to the presence of any number of species, but of course if the experiment were to be meaningful, the molar response coefficients would have to be different for each "channel" or signal. A good example would be a diode array spectrophotometer observing at several different different wavelengths the change of absorbance over time. Hope this helps, -- Petr _____________________________________________________________________ Petr Kuzmic, Ph.D. * BioKin, Ltd. * Consulting & Software Development http://www.biokin.com * (608) 256-4790 * (608) 256-1269 FAX ;------------------------------------------------- ; Tissue factor pathway to thrombin. ; ; Reference: Jones & Mann, J. Biol. Chem. 269, 23367 (1994). ; ; Purpose: ; ; Assuming that factors IIa and mIIa could be observed ; (with response factors 1.0 and 1.2, respectively), show ; the maximum on the [IIa + mIIa] concentration curve. ; Also display concentrations of various intermediates, ; as indicated in the 'monitor' section below. ;------------------------------------------------- [task] data = progress task = simulate [mechanism] IX + TF.VIIa <==> IX.TF.VIIa : k6 k16 IX.TF.VIIa --> TF.VIIa + IXa : k11 X + TF.VIIa <==> X.TF.VIIa : k6 k17 X.TF.VIIa --> TF.VIIa + Xa : k12 X + VIIIa.IXa <==> X.VIIIa.IXa : k6 k18 X.VIIIa.IXa --> VIIIa.IXa + Xa : k13 IX + Xa --> Xa + IXa : k15 V + Xa --> Va + Xa : k1 VIII + Xa --> VIIIa + Xa : k3 V + IIa --> IIa + Va : k2 VIII + IIa --> VIIIa + IIa : k4 II + Va.Xa <==> II.Va.Xa : k6 k19 II.Va.Xa --> Va.Xa + mIIa : k14 mIIa + Va.Xa --> Va.Xa + IIa : k5 VIIIa + IXa <==> VIIIa.IXa : k7 k9 Va + Xa <==> Va.Xa : k8 k10 ; VIIIa.IXa --> : k20 [constants] ; all bimolecular rate constants are micromolar k1 = 20, k2 = 20, k3 = 10, k4 = 20, k5 = 10 k6 = 100, k7 = 10, k8 = 400, k15 = 0.1 k9 = 0.005, k10 = 0.4, k11 = 0.3, k12 = 1.15, k13 = 8.2 k14 = 32, k16 = 24, k17 = 44, k18 = 0.001 k19 = 70 ; k20 = 0.00000002 [concentrations] ; all concentrations are micromolar TF.VIIa = 0.000005 II = 1 V = 0.1, VIII = 0.1, IX = 0.1, X = 0.1 [responses] IIa = 1, mIIa = 1.2 [progress] ; remove semicolon from one of the following three lines ; monitor TF.VIIa, IXa ; monitor II, IIa, mIIa monitor Va, VIII, VIIIa, IX, X, Xa mesh from 0 to 300 step 1 error constant 0 file ./examples/simulate/data/thrombin.txt [output] directory ./examples/simulate/output/thrombin [end] .