CBS Computational Biology Services

Although large-scale modelling is becoming increasingly popular, the set up of small models that aim to investigate a specific question can be extremely useful. This is an area where CBS can be most helpful to its clients. In these kind of models, the capacity to abstract into a small number of reactions the main characteristics of a complex cellular process and the capacity to avoid subjectivity are very important. The lumping process should not introduce the bias of the researcher, as this would determine the behaviour of the model and the answers obtained would be, not the result of an objective mathematical analysis, but instead would reflect the preconceptions of the researcher. As important as the choice of the reactional scheme is the estimation of the parameters of the model, which aggregate many processes, with an high degree of significance.

An example of CBS experience in small-scale modelling can be found in Proc. Natl. Acad. Sci USA, 101, 16774-16779. The model has only 5 reactions and was used to study the inhibition of mitochondrial respiration by nitric oxide (NO). Although mitochondrial respiration entails the participation of more than 80 peptides organized in five complexes, the 5-reaction model reproduced the experimental observations of the NO-dependent inhibition, elucidating the molecular mechanisms involved. In addition, novel interpretations for both the physiological and the pathological consequences of the inhibition of mitochondrial respiration by NO were forwarded.