Learning structural bioinformatics and evolution with a snake puzzle

Wepropose here a working unit for teaching basic concepts of structural bioinformatics and evolution through the example of a wooden snake puzzle, strikingly similar to toy models widely used in the literature of protein folding. In our experience, developed at a Master’s course at the Universidad Autónoma deMadrid (Spain), the concreteness of this example helps to overcome difficulties caused by the interdisciplinary nature of this field and its high level of abstraction, in particular for students coming from traditional disciplines. The puzzle will allow us discussing a simple algorithm for finding folded solutions, through which we will introduce the concept of the configuration space and the contact matrix representation. This is a central tool for comparing protein structures, for studying simple models of protein energetics, and even for a qualitative discussion of folding kinetics, through the concept of the Contact Order. It also allows a simple representation ofmisfolded conformations and their free energy. These concepts will motivate evolutionary questions, which we will address by simulating a structurally constrainedmodel of protein evolution, againmodelled on the snake puzzle. In thisway, we can discuss the analogy between evolutionary concepts and statisticalmechanics that facilitates the understanding of both concepts. The proposed examples and literature are accessible, andwe provide supplementarymaterial (see ‘Data Availability’) to reproduce the numerical experiments. We also suggest possible directions to expand the unit. We hope that this work will further stimulate the adoption of games in teaching practice. Subjects Bioinformatics, Computational Biology, Computer Education, Scientific Computing and Simulation