In Silico Laboratory Experiments using Statistical Model Checking: A new model of the Palytoxin-Induced Pump Channel as Case Study.

Studying biological systems is a difficult but important task. Traditional methods include laboratory experimentation and computer simulations. However, often researchers need to explore important but potentially rare events that are not easily observed or simulated. We use UPPAAL-SMC, a formal verification tool to support a methodology that allows modelling biological systems, specify events and conditions that we want to analyze, and to explore system executions using controlled simulations. We also describe an efficient way to reproduce laboratory experiments in silico. Unlike traditional simulations, we are able to guide the experiment to explore special events and conditions expressing these conditions in temporal logic formulas. We have applied this methodology to create a more detailed model of Palytoxin-induced Na + /K + pump channels than was previously possible. Moreover, we have reproduced experimental protocols and their associated electrophysiological recordings, which has not been done in previous works. As a consequence, we have been able to propose a new diprotomeric model for the PTX-pump complex and study its behaviour. The use of our methodology enabled us to reduce the effort and time to perform this research. It can be used to model other complex biological systems, potentially increasing the productivity of such studies.