Bayesian approaches for modeling protein biophysics




Hines, Keegan

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Proteins are the fundamental unit of computation and signal processing in biological systems. A quantitative understanding of protein biophysics is of paramount importance, since even slight malfunction of proteins can lead to diverse and severe disease states. However, developing accurate and useful mechanistic models of protein function can be strikingly elusive. I demonstrate that the adoption of Bayesian statistical methods can greatly aid in modeling protein systems. I first discuss the pitfall of parameter non-identifiability and how a Bayesian approach to modeling can yield reliable and meaningful models of molecular systems. I then delve into a particular case of non-identifiability within the context of an emerging experimental technique called single molecule photobleaching. I show that the interpretation of this data is non-trivial and provide a rigorous inference model for the analysis of this pervasive experimental tool. Finally, I introduce the use of nonparametric Bayesian inference for the analysis of single molecule time series. These methods aim to circumvent problems of model selection and parameter identifiability and are demonstrated with diverse applications in single molecule biophysics. The adoption of sophisticated inference methods will lead to a more detailed understanding of biophysical systems.




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