Biochemical Equilibrium Research Articles

Alterations in the jejunal microbiota and fecal metabolite profiles of rabbits infected with Eimeria intestinalis

BackgroundRabbit coccidiosis is a major disease caused by various Eimeria species and causes enormous economic losses to the rabbit industry. Coccidia infection has a wide impact on the gut microbiota and intestinal biochemical equilibrium. In the present study, we established a model of Eimeria intestinalis infection in rabbits to evaluate the jejunal microbiota and fecal metabolite profiles.MethodsRabbits in the infected group were orally inoculated with 3 × 103E. intestinalis oocysts. On the eighth day of infection, jejunal contents and feces were collected for 16S rRNA gene sequencing and liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis, respectively. Jejunum tissues were harvested for hematoxylin and eosin (H&E), periodic acid-Schiff (PAS), and immunohistochemistry (IHC) staining.ResultsHistopathological analysis showed that the whole jejunum was parasitized by E. intestinalis in a range of life cycle stages, and PAS staining showed that E. intestinalis infection caused extensive loss of goblet cells. IHC staining revealed that TNF-α expression was higher in the E. intestinalis infection group. Moreover, both the jejunal microbiota and metabolites significantly altered after E. intestinalis infection. At the genus level, the abundances of Escherichia and Enterococcus significantly increased in the infected group compared with the control group, while those of Oscillospira, Ruminococcus, Bacteroides, Akkermansia, Coprococcus, and Sarcina significantly decreased. In addition, 20 metabolites and two metabolic pathways were altered after E. intestinalis infection, and the major disrupted metabolic pathway was lipid metabolism.ConclusionsEimeria intestinalis infection induced intestinal inflammation and destroyed the intestinal homeostasis at the parasitized sites, leading to significant changes in the gut microbiota and subsequent corresponding changes in metabolites.Graphical

EQuilibrator 3.0: a database solution for thermodynamic constant estimation.

eQuilibrator (equilibrator.weizmann.ac.il) is a database of biochemical equilibrium constants and Gibbs free energies, originally designed as a web-based interface. While the website now counts around 1,000 distinct monthly users, its design could not accommodate larger compound databases and it lacked a scalable Application Programming Interface (API) for integration into other tools developed by the systems biology community. Here, we report on the recent updates to the database as well as the addition of a new Python-based interface to eQuilibrator that adds many new features such as a 100-fold larger compound database, the ability to add novel compounds, improvements in speed and memory use, and correction for Mg2+ ion concentrations. Moreover, the new interface can compute the covariance matrix of the uncertainty between estimates, for which we show the advantages and describe the application in metabolic modelling. We foresee that these improvements will make thermodynamic modelling more accessible and facilitate the integration of eQuilibrator into other software platforms.

Is Homeopathy related to Chemical Thermodynamics?

In the present article, biochemical equilibrium is used as a starting point for the application of the Le Chatelier–Broun principle in order to clarify mechanisms of homeopathic treatment. The application of chemical thermodynamics to the main homeopathic principles elucidates the well–known “Law of Similars”. In addition, the theory of intensive dilution of homeopathic remedies is discussed.

Activation of phospholipase A2 by prostaglandin in vitro

Prostaglandins are a diverse family of biological active molecules that are synthesized after liberation of arachnidonic or linolenic acid from the plasma membrane by phospholipase A2 (PLA2). Specific prostaglandins may be pro-inflammatory or anti-inflammatory due to a poorly understood biochemical equilibrium. Some of the anti-inflammatory prostaglandins namely, prostaglandin A1 (PGA1) and prostaglandin E1 (PGE1) have a cyclopentenone moiety that can react and modify a protein’s activity. These two prostaglandins are electrophilic reactive lipid species and are formed as a result of the reaction cascade initiated by PLA2. It was of interest to study the interaction with these prostaglandins as they could either amplify or block this enzyme’s activity. We found that the former is true initially as there is a shorter time to activate the protein on the lipid membrane and an overall increase in hydrolysis was observed when PGA1 and PGE1 prostaglandin was added with PLA2 and liposomes. The interfacial activation model was further explored in which there is a modification of the enzyme rather than a modifcation of the substrate. However, after a time the protein was shown to form amyloid like fibrils thereby blocking further hydrolysis. The fibrillization kinetics in the presence of the one of the prostaglandins was monitored using thioflavin T (ThT) and the resulting fibrils were characterized using transmission electron microscopy (TEM) and atomic force microscopy (AFM). Modification of PLA2 by these prostaglandins leading to amyloid like fibrils gives an additional perspective of control of the interfacial activation mechanism of this enzyme.

The effect of microplastics pollution in microalgal biomass production: A biochemical study

Microplastics (MPs) are widely spread throughout aquatic systems and water bodies. Given that water quality is one of the most important parameters in the microalgal-based industry, it is critical to assess the biochemical impact of short- and long-term exposure to MPs pollution. Here, the microalga Phaeodactylum tricornutum was exposed to water contaminated with 0.5 and 50 mg L−1 of polystyrene (PS) and/or polymethyl methacrylate (PMMA). Results show that the microalgal cultures exposed to lower concentrations of PS displayed a growth enhancement of up to 73% in the first stage (days 3-9) of the exponential growth phase. Surprisingly, and despite the fact that long-term exposure to MPs contamination did not impair microalgal growth, a steep decrease in biomass production (of up to 82%) was observed. The production of photosynthetic pigments was shown to be pH-correlated during the full growth cycle, but cell density-independent in later stages of culturing. The extracellular carbohydrates production exhibited a major decrease during long-term exposure. Still, the production of extracellular proteins was not affected by the presence of MPs. This pilot laboratory-scale study shows that the microalgal exposure to water contaminated with MPs disturbs its biochemical equilibrium in a time-dependent manner, decreasing biomass production. Thus, microalgal industry-related consequences derived from the use of MPs-contaminated water are a plausible possibility.

Сравнительная оценка антиоксидантного и прооксидантного статуса в процессе роста культивируемых растительных клеток двух штаммов Polyscias filicifolia и Polyscias filicifolia LX-5

Сell cultures of plants are widely used as a model, which allows to evaluate adequately the metabolic processes in plants and their responses to various external influences, to study many physiological and biochemical processes in plants. It is known that cells actively proliferating outside the body contain a high level of activity of antioxidant enzymes. During the process of dividing cultured cells in the presence of oxygen, free oxygen radicals are generated, the excess of which is controlled by a reliable antioxidant defense system. Therefore, the assessment of biochemical equilibrium in this system, in our opinion, can be an objective marker indicator of the physiological stability of cells, which is extremely important, both theoretically and practically. In recent years, studies of organogermanium compounds with low toxicity and a wide spectrum of biological activity are one of the promising trends in modern chemistry of organogermanium compounds. In our study, it was shown that the activity of antioxidant enzymes in callus cells increased on average by 11% (SOD), 18.6% (peroxidase) and 26.5% (catalase) after polyscias tissue culture being transferred to a selective medium enriched with germanium by an organic compound. In the process of growth of cells of the initial and selective polyscias strains, the oscillatory nature of the change in the catalytic activity of the three main enzymes of the antioxidant system can be noted. The nature of these changes correlated with changes in the mitotic activity of the cells. The degree of oxidative modification of proteins in cells of both strains of polyscias tissue culture also correlated with the level of their mitotic activity.

Inductively Coupled Plasma Optical Emission Spectrometry (ICP‐OES) Analysis of Lead Bioaccumulation in Chlamydomonas reinhardtii and the Role of Cia7 Gene

The indiscriminate use of heavy metals in human activities has become a threat for the biochemical equilibrium and geochemical cycles of nature. To survive in heavy‐metal polluted environments, some microorganisms have developed a variety of detoxifying mechanisms. An excellent model organism for the study of heavy metal tolerance and homeostasis is Chlamydomonas reinhardtii, a unicellular green haploid microalga. The purpose of this research project was to identify the function of the novel gene Cia7 in C. reinhardtii, and specifically, to determine if it has a role in heavy metal tolerance. It was hypothesized that wild type C. reinhardtii (CC4425) would exhibit less bioaccumulation and higher resistance heavy metal stress; while a mutant strain in which Cia7 has been suppressed (CC5013), would exhibit inhibited growth and higher metal bioaccumulation compared to the wild type. In this study, both strains of C. reinhardtii were treated with either 0 μM or 150 μM of Pb(NO3)2 solution. Lead bioaccumulation after three days of treatment was determined by inductively coupled plasma optical emission spectrometry (ICP‐OES). Chlorophyll concentration and cell growth analysis were also performed. Both strains of C. reinhardtii were treated with increasing concentrations of lead, and absorbance readings at 663, 645, 730 nm were taken on 3‐day intervals over a 15‐day treatment period. Results from ICP‐OES analysis showed no difference in lead bioaccumulation between both strains. The wild type strain (CC4425) demonstrated a relatively higher growth rate than the mutant (CC5013). Chlorophyll concentration and growth in the wild type strain decrease as the concentration of lead in solution increases. On the other hand, chlorophyll concentration and growth in the mutant strain was observed to increase with a higher treatment of lead.Support or Funding InformationACT on Ideas ‐ Texas A&M International University/College of Arts and Sciences ‐ Texas A&M International UniversityThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A Homeopathy Model in the Light of Hahnemann’s Pristine Idea

The well-known definition of disease, which Samuel Hahnemann presented while making a challenge to provide a tentative theory for his new science and art of healing, is used as a starting point for the model. The biochemical equilibrium is used for a demonstration of the Le Chatelier-Braun principle and/or the Guldberg–Waage Law in order to clarify the principles and to explain the well-known “Law of Similar”. It is shown that a high dilution accompanied by succession is required to release the remedies to their constituent molecular species in order to increase their “vital energy” when taking part in the overall complex biochemical equilibrium that is essential for healing. In addition, it is revealed that, in principle, a single remedy constituent molecular species, when it is in excess, as well as satisfying the dynamic equilibrium, can shift this biochemical equilibrium and trigger the healing process.

Evaluation of energy metabolism and calcium homeostasis in cells affected by Shwachman-Diamond syndrome.

Isomorphic mutation of the SBDS gene causes Shwachman-Diamond syndrome (SDS). SDS is a rare genetic bone marrow failure and cancer predisposition syndrome. SDS cells have ribosome biogenesis and their protein synthesis altered, which are two high-energy consuming cellular processes. The reported changes in reactive oxygen species production, endoplasmic reticulum stress response and reduced mitochondrial functionality suggest an energy production defect in SDS cells. In our work, we have demonstrated that SDS cells display a Complex IV activity impairment, which causes an oxidative phosphorylation metabolism defect, with a consequent decrease in ATP production. These data were confirmed by an increased glycolytic rate, which compensated for the energetic stress. Moreover, the signalling pathways involved in glycolysis activation also appeared more activated; i.e. we reported AMP-activated protein kinase hyper-phosphorylation. Notably, we also observed an increase in a mammalian target of rapamycin phosphorylation and high intracellular calcium concentration levels ([Ca2+]i), which probably represent new biochemical equilibrium modulation in SDS cells. Finally, the SDS cell response to leucine (Leu) was investigated, suggesting its possible use as a therapeutic adjuvant to be tested in clinical trials.

A Homeopathy Model in the Light of Hahnemann’s Pristine Idea

The well-known definition of disease, which Samuel Hahnemann presented while making a challenge to provide a tentative theory for his new science and art of healing, is used as a starting point for the model. The biochemical equilibrium is used for a demonstration of the Le Chatelier–Braun principle and/or the Guldberg–Waage Law in order to clarify the principles and to explain the well-known “Law of Similar”. It is shown that a high dilution accompanied by succussion is required to release the remedies to their constituent molecular species in order to increase their “vital energy” when taking part in the overall complex biochemical equilibrium that is essential for healing. In addition, it is revealed that, in principle, a single remedy constituent molecular species, when it is in excess, as well as satisfying the dynamic equilibrium, can shift this biochemical equilibrium and trigger the healing process.

Anaerobic digestion of bio-waste: A mini-review focusing on territorial and environmental aspects

Scientific and industrial experiences, together with economical and policies changes of last 30 years, bring anaerobic digestion among the most environmental friendly and economically advantageous technologies for organic waste treatment and management in Europe. In this short review, the role of anaerobic digestion of organic wastes is discussed, considering the opportunity of a territorial friendly approach, without barriers, where different organic wastes are co-treated. This objective can be achieved through two proposed strategies: one is the anaerobic digestion applied as a service for the agricultural and farming sector; the other as a service for citizen (biowaste, diapers and wastewater treatment integration). The union of these two strategies is an environmental- and territorial-friendly process that aims to produce renewable energy and fertiliser material, with a low greenhouse gas emission and nutrients recovery. The advantage of forthcoming application of anaerobic digestion of organic wastes, even for added value bioproducts production and new energy carriers, are finally discussed. Among several advantages of anaerobic digestion, the role of the environmental controller was evaluated, considering the ability of minimising the impacts exploiting the biochemical equilibrium and sensitivity as a quality assurance for digestate.

A new hypothesis on preventable neuropsychiatric illness in Africa

BackgroundCommunicable diseases are still the most important public health challenge in Africa. Many of them such as malaria, schistosomiasis and pneumonia are frequently treated with quinoline derived substances, which are known to have neuropsychiatric side effects.Millions of Africans have to take two or three of them simultaneously (e.g. quinine and ciprofloxacin or praziquantel). Almost nothing is known about their additive effects or interactions. HypothesisWe hypothesize, that a parallel therapy with quinoline derived antimicrobial substances leads to a preventable neuropsychiatric syndrome and suggest to find the joint pathobiochemical explanation for this condition in the l-Tryptophane–Kynurenine–Serotonine pathway. DiscussionAlmost all intermediary substances of the Kynurenine pathway (tryptophan, kynurenine, kynurenic acid, quinolinic acid and serotonin) are known to have neuropsychiatric properties on their own.Direct interactions between quinolines and the oxygenases of the pathway (especially with the indoleamine (2,3)-dioxygenase and kynurenine-monoxygenase) and indirect influences via the interferon-γ induced breakdown of tryptophane are discussed, as well as the modifying effect of the already existing neurotoxicity of the single quinoline related drug used.Three different mechanisms were discovered which can influence the complex, well balanced biochemical equilibrium of the kynurenine pathway. Due to the complexity of the pathway and the fact that all substances have their own, even contradictory, neuropsychiatric properties, we do not argue that through a certain type of postulated metabolism a certain drug might have a specific effect, but we do hypothesize that it is the disturbance of a well balanced equilibrium which makes a neuropsychiatric effect of the parallel antimicrobial therapy with quinolines more than probable. ConsequencesIf confirmed, our hypothesis demonstrates that parallel therapy with quinoline antimicrobials constitutes an under addressed public health challenge in Africa with severe diagnostic, therapeutic and financial implications.The individual physician has to take a new entity into account for the neuropsychiatric differential diagnosis, especially in patients suffering from another neurological illness, being treated with efavirenz or belonging to high risk groups affecting the health of others like mini-bus drivers.Further direct consequences apply to physicians in the rich countries dealing with migrants, refugees, long term expats or professional groups in need of a high level of psychological stability, good judgement and fine motor skills. ConclusionThe hypothesis needs urgent confirmation in a randomized, prospective trial comparing levels of quinolinic acid etc., in patients on quinoline treatment versus a quinoline-naïve patients for several body fluids and ideally in the brain post-mortem.

Human and Animal Brain Phospholipids Fatty Acids, Evolution and Mood Disorders

The purpose of this paper is to connect the experimental evidence concerning brain phospholipids fatty acids composition by comparing the first warm-blooded animal in the phylogeny (birds) with the human brain at various ages of life (from the fetal period until the eightieth year of age). The particularity of our investigation is an almost unique opportunity for groped a hypothesis about the evolutionary aspects of the behavior of brain and consciousness, as represented in the human and animal world, as a result of the evidence that led to the diagnostic classification of mood disorders in humans, in their similarity with some animal species. A logical sequence of considerations about the mood disorder diagnosis, due to unequivocal evidence by the use of mathematical tools that cannot be manipulated, it leads to results that most probably indicate and suggest the existence of a common brain “biochemical house“, in man and animal. This “common house” will become more and more complex, during evolution, from animal to man, respecting the concept of the molecular equilibrium and allowing to each living being the adaptation to their needs and their roles. Small deviations from the biochemical equilibrium of brain fatty acids can manifest pathological behavioral responses, much amplified. Everything seems to be witnessed by the strong classificatory correspondence of the platelets fatty acids which correspond to psycho pathologies, especially for the Linoleic acid and alpha Linolenic acid, in particular the Linoleic Acid, which, to varying percentages, it may correspond to psychopathological phenomena.

Quantitative multi-color FRET measurements by Fourier lifetime excitation-emission matrix spectroscopy

Förster resonant energy transfer (FRET) is extensively used to probe macromolecular interactions and conformation changes. The established FRET lifetime analysis method measures the FRET process through its effect on the donor lifetime. In this paper we present a method that directly probes the time-resolved FRET signal with frequency domain Fourier lifetime excitation-emission matrix (FLEEM) measurements. FLEEM separates fluorescent signals by their different phonon energy pathways from excitation to emission. The FRET process generates a unique signal channel that is initiated by donor excitation but ends with acceptor emission. Time-resolved analysis of the FRET EEM channel allows direct measurements on the FRET process, unaffected by free fluorophores that might be present in the sample. Together with time-resolved analysis on non-FRET channels, i.e. donor and acceptor EEM channels, time resolved EEM analysis allows precise quantification of FRET in the presence of free fluorophores. The method is extended to three-color FRET processes, where quantification with traditional methods remains challenging because of the significantly increased complexity in the three-way FRET interactions. We demonstrate the time-resolved EEM analysis method with quantification of three-color FRET in incompletely hybridized triple-labeled DNA oligonucleotides. Quantitative measurements of the three-color FRET process in triple-labeled dsDNA are obtained in the presence of free single-labeled ssDNA and double-labeled dsDNA. The results establish a quantification method for studying multi-color FRET between multiple macromolecules in biochemical equilibrium.

Responses of CYP450 dependent system to aliphatic and aromatic hydrocarbons body burden in transplanted mussels from South coast of Portugal

Mussels Mytilus galloprovincialis were cross-transplanted at South Portugal from a reference site (site 1) to a site more contaminated with hydrocarbon compounds (site 2), and vice versa, in an active biomonitoring (ABM) concept, to assess the biotransformation capacity catalyzed by the mixed function oxygenase (MFO) system. Total alkanes (TAlk), the unresolved complex mixture (UCM), and total polycyclic aromatic hydrocarbons (TPAHs) concentration increased respectively 6, 4.4 and 4.2 fold relatively to control, in mussels transplanted from site 1 to 2. In the cross-transplant, a 48, 57 and 62% depuration of TAlk, UCM and TPAHs concentrations occurred by the end of the 3-4th week. Petrogenic and biogenic (marine and terrigenous) sources of AHs, and petrogenic and pyrolitic (biomass and oil/fuel incomplete combustion) sources of PAHs were detected at both sites. CYP450, CYT b (5) and NADPH-RED in mussels transplanted from site 1 to 2 were induced from day 0 to 28, with a total increase of 35, 32 and 35%, respectively, while biochemical equilibrium to lesser environmental contamination occurs in mussels transplanted from site 2 to 1. A significant relationship between CYP450 and NADPH-RED was found with TPAH, with distinctive behavior at the two sites. MFO system components increase with exposure time at one site and decreases in the other, reflecting an adaptation to distinct environmental hydrocarbon loads. The ABM strategy proved to be useful to understand the environment real impact on the biochemical responses in mussels' local populations. In this study, CYP450 and NADPH-RED are a useful biomarker for hydrocarbon exposure.

Mood Disorders and the Brain: Depression, Melancholia, and the Historiography of Psychiatry

Despite the increasingly widespread availability of psychotropics believed to restore biochemical equilibrium in the brains of persons diagnosed with mood disorders, the number of people suffering from such medical conditions appears to be increasing. According to The Royal College of Psychiatrists, ‘by 2020 it is estimated that depression will be the second most common disabling condition in the world’, a figure it derives from the World Health Organization. Depression is, it seems, rapidly becoming a global threat. In a trend that is mirrored in much of the West, the number of prescriptions dispensed for antidepressants in the UK has doubled in the last decade and is continuing to rise. The need for a critical perspective on mood disorders is growing.

Intra-annual variation in biochemical properties and the biochemical equilibrium of different grassland soils under contrasting management and climate

In this study, the effects of different management practices on soil biochemical properties were evaluated in three pairs of grassland soils (unmanaged and managed) located in three areas of Galicia (NW Spain) where different types of climate prevail. Variations in soil biochemical properties were monitored throughout 1 year. Changes in soil temperature, soil moisture content, and particularly soil location and soil management affected the values of the biochemical properties. Comparatively higher levels of enzyme activity were observed in the unmanaged grasslands than in the managed grasslands, especially for β-glucosidase activity and the enzymes involved in the P and S cycles (phosphodiesterase, phosphomonoesterase, and arylsulphatase activities). A biochemical equilibrium index was used to evaluate soil quality. Although variations in the index were observed throughout the year, the values mainly depended on soil management and revealed that unmanaged grasslands were in a situation of biochemical equilibrium throughout the study period, while no such equilibrium was observed in managed grasslands for most of the studied period.

Biochemical properties in managed grassland soils in a temperate humid zone: modifications of soil quality as a consequence of intensive grassland use

Although soil biochemical properties are considered to be good indicators of changes in soil quality, few studies have been made of the changes in biochemical properties brought about by anthropogenic disturbance of grassland ecosystems. In the present study, several biochemical properties were analysed in 31 grassland soils subjected to a high level of management, and the values obtained were compared with known values corresponding to native grasslands from the same region (Galicia, NW Spain). The 31 managed grasslands were divided into two groups (re-sown grasslands and improved grasslands) according to their management and past land use. The biochemical properties studied were: labile carbon, microbial biomass carbon, microbial respiration, metabolic quotient, net nitrogen mineralisation and the activities of dehydrogenase, catalase, phosphodiesterase, phosphomonoesterase, casein hydrolysing proteases, benzoyl arginamide (BAA)-hydrolysing proteases, urease, cellulase, s-glucosidase, invertase and arylsulphatase. Managed grasslands exhibited lower values of soil biochemical properties than native grasslands. Three biochemical equilibrium equations were used to compare soil quality in managed and native grasslands. One of the equations did not show any significant difference between the groups of grassland soils considered. In contrast, two of the equations showed similar soil quality for improved and native grasslands, while re-sown grasslands exhibited a loss of soil quality when compared to native grassland soils.

Exercise and Fatigue

Physical exercise affects the equilibrium of the internal environment. During exercise the contracting muscles generate force or power and heat. So physical exercise is in fact a form of mechanical energy. This generated energy will deplete the energy stocks within the body. During exercise, metabolites and heat are generated, which affect the steady state of the internal environment. Depending on the form of exercise, sooner or later sensations of fatigue and exhaustion will occur. The physiological role of these sensations is protection of the exercising subject from the deleterious effects of exercise. Because of these sensations the subject will adapt his or her exercise strategy. The relationship between physical exercise and fatigue has been the scope of interest of many researchers for more than a century and is very complex. The exercise intensity, exercise endurance time and type of exercise are all variables that cause different effects within the body systems, which in turn create different types of sensation within the subject's mind during the exercise. Physical exercise affects the biochemical equilibrium within the exercising muscle cells. Among others, inorganic phosphate, protons, lactate and free Mg2+ accumulate within these cells. They directly affect the mechanical machinery of the muscle cell. Furthermore, they negatively affect the different muscle cell organelles that are involved in the transmission of neuronal signals. The muscle metabolites produced and the generated heat of muscle contraction are released into the internal environment, putting stress on its steady state. The tremendous increase in muscle metabolism compared with rest conditions induces an immense increase in muscle blood supply, causing an increase in the blood circulatory system and gas exchange. Nutrients have to be supplied to the exercising muscle, emptying the energy stocks elsewhere in body. Furthermore, the contracting muscle fibres release cytokines, which in their turn create many effects in other organs, including the brain. All these different mechanisms sooner or later create sensations of fatigue and exhaustion in the mind of the exercising subject. The final effect is a reduction or complete cessation of the exercise. Many diseases speed up the depletion of the energy stocks within the body. So diseases amplify the effect of energy stock depletion that accompanies exercise. In addition, many diseases produce a change of mind-set before exercise. These changes of mind-set can create sensations of fatigue and exercise-avoiding behaviour at the onset of an exercise. One might consider these sensations during disease as a feed-forward mechanism to protect the subject from an excessive depletion of their energy stocks, to enhance the survival of the individual during disease.

Equilibrium model selection: dTTP induced R1 dimerization

BackgroundBiochemical equilibria are usually modeled iteratively: given one or a few fitted models, if there is a lack of fit or over fitting, a new model with additional or fewer parameters is then fitted, and the process is repeated. The problem with this approach is that different analysts can propose and select different models and thus extract different binding parameter estimates from the same data. An alternative is to first generate a comprehensive standardized list of plausible models, and to then fit them exhaustively, or semi-exhaustively.ResultsA framework is presented in which equilibriums are modeled as pairs (g, h) where g = 0 maps total reactant concentrations (system inputs) into free reactant concentrations (system states) which h then maps into expected values of measurements (system outputs). By letting dissociation constants Kd be either freely estimated, infinity, zero, or equal to other Kd, and by letting undamaged protein fractions be either freely estimated or 1, many g models are formed. A standard space of g models for ligand-induced protein dimerization equilibria is given. Coupled to an h model, the resulting (g, h) were fitted to dTTP induced R1 dimerization data (R1 is the large subunit of ribonucleotide reductase). Models with the fewest parameters were fitted first. Thereafter, upon fitting a batch, the next batch of models (with one more parameter) was fitted only if the current batch yielded a model that was better (based on the Akaike Information Criterion) than the best model in the previous batch (with one less parameter). Within batches models were fitted in parallel. This semi-exhaustive approach yielded the same best models as an exhaustive model space fit, but in approximately one-fifth the time.ConclusionComprehensive model space based biochemical equilibrium model selection methods are realizable. Their significance to systems biology as mappings of data into mathematical models warrants their development.