Team:Heidelberg/Modeling
Modeling
In our subprojects on the development of switchable AptaBodies and on aptamer-based small-molecule sensing, we wanted to determine affinities and kinetic parameters of enzymes. For this purpose, we constructed mathematical models of coupled ordinary differential equations (ODEs) and used experimental data for parameter estimations.
Thereby, we could successfully characterize affinities of switchable AptaBodies to their targets. The estimated parameters could be complemented by theoretical stem strengths that were predicted from our molecular dynamics simulations. With regard to our in-vitro transcription subproject, we could test different hypotheses on the function of a polymerase based on model selection. We learned that the binding kinetics of the polymerase to its target is an important determinant for the transcription kinetics. The surprising result that increasing the concentration of the polymerase results in a hyper-linear gain of products could be mechanistically verified by a decrease of polymerase accuracy at higher ATP to polymerase ratios. In the following the two models shall be described.
Assisting the optimization of switchable aptamer sensors by mathematical modeling
Studying determinants of polymerase efficiency based on an aptamer sensor